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KCNH2 mutation c.3099_3112del causes congenital long QT syndrome type 2 with gender differences
ZunPing Kea, Chao Lib, Gang Baic, Li Tand, JunFeng Wangd, Ming Zhoud, JianHua Zhoud, Shi-You Chene, Xiao Dongd,e,
Corresponding author
a School of Public Health, Hubei University of Medicine, China
b Children's Medical Center, Taihe Hospital, Hubei University of Medicine, China
c Department of Ultrasonics, Taihe Hospital, Hubei University of Medicine, China
d Cardiovascular Center, Taihe Hospital, Hubei University of Medicine, China
e Department of Surgery, University of Missouri School of Medicine, Columbia, MO, USA
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0007">Introduction</span><p id="para0006" class="elsevierStylePara elsevierViewall">Long QT Syndrome &#40;LQTS&#41; is an inherited primary arrhythmia syndrome with a prevalence of&#160;1 in every&#160;2000&#160;healthy live births&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> This autosomal dominant inherited disease causes palpitation&#44; dizziness&#44; syncope&#44; and anoxic seizures secondary to ventricular arrhythmia&#44; classically torsade de pointes with a risk of sudden death&#46; There are&#160;17&#160;different subtypes of LQTS associated with monogenic mutations of&#160;15&#160;autosomal dominant genes&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> Mutations in these genes adversely affect cardiac ion channels&#44; resulting in delayed repolarization of cardiomyocyte action potential and manifesting as prolonged QT intervals in the surface electrocardiogram&#46; Based on the studies from Mayo&#39;s LQTS Clinic&#44;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> there is substantial overlap in the distribution of QTc between healthy subjects and patients with genetically confirmed LQTS&#44; which makes the diagnosis of LQTS challenging&#46; Genetic testing of cardiac ion channelopathy mutations is now recommended as an essential component for diagnosis and familial cascade screening of LQTS patients&#46;</p><p id="para0007" class="elsevierStylePara elsevierViewall">LQT2 is the second most common subtype of LQTS&#44; affecting approximately&#160;30&#160;&#37; of congenital LQTS individuals&#46; Genetic tests identify mutations of potassium voltage-gated channel subfamily H member&#160;2 &#40;KCNH2&#41; involved in the reduction of IKr amplitudes which causes LQT2&#46; Up to date&#44; around&#160;900&#160;mutations in the KCNH2 gene have been reported in the Human Gene Mutation Database &#40;HGMD&#41;&#46; However&#44; due to a paucity of gene- and variant-level evidence&#44; only a small number of these mutations are found to be related to the clinical features&#46; Ongoing efforts in the study of genotype&#44; phenotype&#44; mutation topology&#44; and clinical therapies are important to reduce the risk of misinterpretation and diagnostic miscues&#46;</p><p id="para0008" class="elsevierStylePara elsevierViewall">In this study&#44; we described the genotype&#44; clinical&#44; and ECG manifestations of a Chinese Han family with LQTS2&#46; Targeted gene capture and next-generation sequencing were used to identify a deletion mutation&#44; KCNH2&#40;NM&#95;000238&#46;3&#41;&#58; c&#46;3099&#95;3112del&#44; in exon&#160;13 of the KCNH2 gene&#46; We further predicted three-dimensional structures of mutated protein using the homologous modeling method&#46; Lidocaine attenuation testing was performed to investigate the therapeutic reaction to antiarrhythmic drugs&#46; Cardiac events and ventricular tachycardia episodes were recorded with a three-year follow-up after dual chamber Implantable Cardioverter-Defibrillator &#40;ICD&#41; pacemaker implantation&#46; Our clinical investigation of this pathological mutation provided new insight into the pathogenesis of LQTS and assisted the therapeutic decision&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Patients and methods</span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Ethics statement</span><p id="para0009" class="elsevierStylePara elsevierViewall">This study was approved by the Medical Ethics Committee of Taihe Hospital&#44; Hubei University of Medicine&#46; All procedures were in accordance with the &#8220;Declaration of Helsinki&#8221; and the ethical standards of the Responsible Committee on human experimentation&#46; Informed consent was obtained from all subjects or their legal guardians&#46; The proband has provided informed consent for publication of the case&#46;</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Proband and family investigation</span><p id="para0010" class="elsevierStylePara elsevierViewall">The proband was a&#160;31-year-old Chinese Han female&#44; who was born at full term after a normal pregnancy and delivery&#46; She was referred from a local hospital to Hubei University of Medicine affiliated Taihe Hospital because of recurrent ventricular tachycardia and ventricular fibrillation lasting for one day on June&#160;6&#44; 2017&#46; She had experienced numerous palpitations&#44; amaurosis&#44; and syncope in the last&#160;3-years&#44; and the episodes usually occurred in the morning when there was a sudden loud noise during her sleep&#44; and the episodes always appeared during her menstrual period&#46; The symptoms recurred&#160;2 weeks earlier and deteriorated for&#160;2 days before she went to a local hospital&#46; Potassium supplementation therapy was provided immediately in the local hospital&#44; and defibrillation was given&#160;3&#160;times&#47;day to treat the recurrent ventricular fibrillation&#46;</p><p id="para0011" class="elsevierStylePara elsevierViewall">After being transferred to our hospital&#44; further laboratory tests and other examinations were performed&#44; and electrocardiographic activities were monitored during medication&#46; A family history investigation revealed that no similar symptoms were detected in other members&#46; Eight individuals were enrolled for clinical and genetic studies and underwent a full physical examination&#44; including QT interval assessment and T-wave morphology through ECG&#46; The QT intervals were measured by the Tangent method and calculated by the Bazett correction formula&#44; which gave the rate-corrected QT &#40;QTc&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> The family members were clinically diagnosed as LQTS if they had a prolonged QT interval &#40;QTc&#160;&#8805; 470&#160;ms for males&#59; QTc&#160;&#8805; 480&#160;ms for females&#41; or risk score&#160;&#8805; 4&#160;according to the Schwartz scoring scale&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a><a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> The family pedigree was shown in <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">Lidocaine attenuation testing</span><p id="para0012" class="elsevierStylePara elsevierViewall">To investigate the patient&#39;s sensitivity to lidocaine&#44; we performed a Lidocaine Attenuation Test &#40;LAT&#41; in a fasting state&#46; Before intravenous infusion of lidocaine&#44; the baseline QT&#44; QTc&#44; and RR intervals were obtained&#46; Then&#44; 2&#160;mg&#47;kg of lidocaine was infused with an intravenous line for&#160;10&#160;minutes followed by an infusion of&#160;4&#160;mg&#47;min of lidocaine for&#160;2&#160;hours&#46; QT intervals&#44; RR intervals&#44; and the derived Bazett&#39;s heart rate-corrected QTc values were recorded after the first&#160;10-min infusion followed by recordings at&#160;15-minute intervals for&#160;2&#160;hours&#46; QT intervals were measured by the Tangent method as described above&#46; All values were obtained from lead V5 as a mean of&#160;3&#160;consecutive beats&#46; The LAT is considered positive if the QTc interval is shortened by&#160;&#8805; 30&#160;ms from baseline at any time point during the infusion according to Anderson&#39;s study&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Next-generation sequencing &#40;NGS&#41; and sanger sequencing</span><p id="para0013" class="elsevierStylePara elsevierViewall">Next-generation sequencing was performed on the proband &#40;III-8 in <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>&#41;&#44; her father&#44; and her mother&#46; Four milliliters of peripheral blood were collected and used to isolate genomic DNA &#40;QIAamp DNA Mini kit&#44; Qiagen GmbH&#41;&#46; Target sequences were enriched using customized capture probes chips targeting&#160;15&#160;genes associated with LQTS&#44; i&#46;e&#46;&#44; potassium voltage-gated channel subfamily Q member&#160;1 &#40;KCNQ1&#41;&#44; potassium voltage-gated channel subfamily H member&#160;2 &#40;KCNH2&#41;&#44; sodium voltage-gated channel alpha subunit&#160;5 &#40;SCN5A&#41;&#44; Ankyrin&#160;2 &#40;ANK2&#41;&#44; potassium voltage-gated channel subfamily E regulatory subunit&#160;1 &#40;KCNE1&#41;&#44; potassium voltage-gated channel subfamily E regulatory subunit&#160;2 &#40;KCNE2&#41;&#44; potassium inwardly-rectifying channel subfamily J member&#160;2 &#40;KCNJ2&#41;&#44; calcium voltage-gated channel subunit alpha&#160;1 C &#40;CACNA1C&#41;&#44; Caveolin&#160;3 &#40;CAV3&#41;&#44; sodium voltage-gated channel beta subunit&#160;4 &#40;SCN4B&#41;&#44; A-Kinase Anchoring Protein&#160;9 &#40;AKAP9&#41;&#44; Syntrophin Alpha&#160;1 &#40;SNTA1&#41;&#44; potassium inwardly rectifying channel subfamily J member&#160;5 &#40;KCNJ5&#41;&#44; Calmodulin&#160;1 &#40;CALM1&#41;&#44; and Calmodulin&#160;2 &#40;CALM2&#41;&#46; Genomic DNA was fragmented on an E220 focused ultrasonicator &#40;Covaris&#44; Inc&#46;&#41;&#44; then captured by custom-designed DNA probes &#40;Agilent Technologies&#44; Inc&#46;&#41; and amplified by PCR&#46; The final products were sequenced with&#160;150-bp paired-end reads on the Illumina Nextseq&#160;500&#160;platform&#46; All identified variants were annotated according to the guidelines published by the Human Genome Variation Society &#40;HGVS&#44; <a href="http://www.hgvs.org/content/guidelines">http&#58;&#47;&#47;www&#46;hgvs&#46;org&#47;content&#47;guidelines</a>&#41;&#46;</p><p id="para0014" class="elsevierStylePara elsevierViewall">Sanger sequencing was performed to confirm the potential pathogenic variants and to segregate them among family members&#46; The specific PCR primers &#40;Forward primer 5&#8217;-TCTACCCCGCTCACCCAG-3&#8217;&#44; Reverse primer 5&#8217;-TCTCCCTCTACCAGACAACACC-3&#8217;&#41; were used for the amplification of exon&#160;13 in Kthe CNH2 gene based on the reference sequences of the human genome from GenBank in NCBI &#40;NC&#95;000007&#46;14&#41;&#46; Genomic DNA was first denatured at&#160;94&#176;C for&#160;5 minutes&#44; followed by&#160;30&#160;cycles of&#160;98&#176;C for&#160;10&#160;seconds&#44; 60&#176;C for&#160;35&#160;seconds&#44; and 72&#176;C for&#160;60&#160;seconds&#46; The PCR products were extended at&#160;72&#176;C for&#160;5&#160;minutes&#46; The products were gel-purified and sequenced using the forward and reverse primers&#46; Automated sequencing was performed at both ends on an ABI&#160;377&#160;automatic sequencer&#46; NGS and Sanger sequencing were completed by Sino Path Diagnosis &#40;Beijing&#44; China&#41;&#46;leted by Sino Path Diagnosis &#40;Beijing&#44; China&#41;&#46;</p></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013">ICD implantation</span><p id="para0015" class="elsevierStylePara elsevierViewall">Under local anesthesia with lidocaine&#44; implantation of the ICD system &#40;Medtronic&#44; D284DRG&#44; PZM626455S&#41; was undertaken using standard techniques&#46; The ventricular lead &#40;6944-65cm&#44; TDC122150V&#41; tip with defibrillation coil was positioned in the apex of the right ventricle&#44; and the position was confirmed by a single shot of fluoroscopy&#46; The right atrial lead &#40;4574-53cm&#44; BBE183554G&#41; was placed in the right auricle whilst continued to check on the location of the ventricle lead by fluoroscopy to maintain it in the correct position &#40;Supplemental Fig&#46; 1&#41;&#46; All the lead pacing&#47;sensing parameters were recorded&#46;</p></span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014">Follow up</span><p id="para0016" class="elsevierStylePara elsevierViewall">The patient was convalesced and discharged with a prescription of propranolol &#40;10&#160;mg three times a day&#41; and mexiletine &#40;150&#160;mg three times a day&#41;&#46; At the&#160;3&#160;months&#44; 1&#160;year&#44; and 3&#160;year follow-ups&#44; pacemaker-recorded parameters &#40;such as threshold&#44; R wave amplitude and impedance&#41; and events &#40;such as ventricular fibrillation and heart beating stop&#41; were examined&#46; The ambulatory Holter monitoring&#44; and echocardiography were performed and analyzed&#46;</p></span></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0015">Results</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0016">Clinical abnormality of patients with LQTS</span><p id="para0017" class="elsevierStylePara elsevierViewall">12-lead ECG of the proband performed in the local hospital demonstrated recurrent paroxysmal ventricular tachycardia&#44; and torsade de pointes &#40;Supplemental Fig&#46; 2&#160;A&#8210;C&#41;&#46; Electrolyte analyses showed that potassium and Magnesium were in the normal lower limit &#40;K<span class="elsevierStyleSup">&#43;</span>&#44; 3&#46;68&#160;mmoL&#47;L&#59; Mg<span class="elsevierStyleSup">2&#43;</span>&#44; 0&#46;77&#160;mmoL&#47;L&#41; while NT-proBNP&#44; blood glucose&#44; coagulation function&#44; blood cell count&#44; CRP&#44; arterial blood gas&#44; thyroid function&#44; CKMB&#44; troponin&#44; renal and liver function were all in normal ranges&#46;</p><p id="para0018" class="elsevierStylePara elsevierViewall">12-lead ECG performed in Taihe Hospital showed a short PR interval of&#160;110&#160;ms and prolonged QTc interval of&#160;523&#160;ms &#40;Supplemental Fig&#46; 2D&#41;&#46; Transthoracic echocardiography showed normal cardiac structure with the ejection fraction in normal lower limit &#40;EF&#160;&#37;&#160;&#61;&#160;53&#160;&#37;&#44; Supplemental Fig&#46; 3&#41;&#46; 24h-ambulatory Holter monitoring recorded&#160;8796&#160;ventricular premature beats&#44; 146&#160;episodes paroxysmal ventricular tachycardias&#44; and frequent torsade de pointes with some of them evolved to ventricular fibrillations &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>&#41;&#46; The average heart rate in&#160;24&#160;hours was&#160;68&#160;beats&#47;minute&#46; The expression levels of antibodies of MPO&#44; PR3&#44; RF&#44; dsDNA&#44; nucleosome&#44; SmD1&#44; SSA&#44; Scl70&#44; Jo1 were all in the normal ranges &#40;data not shown&#41;&#46; Normal coronary artery was confirmed by enhanced cardiac Computed Tomography &#40;CT&#41; scan&#46; Different T-wave morphology of the proband and family members were showed in <a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>&#44; the female proband had a low amplitude and bifid T-wave&#44; whereas&#160;2&#160;male mutation carriers had high amplitude and notch T-wave&#46; Clinical characteristics of all available family members are summarized in <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#46; The female proband and her son showed short PR intervals &#40;110&#160;ms&#44; 103&#160;ms&#41;&#44; whereas her father&#39;s PR interval was in normal range &#40;123&#160;ms&#41;&#46; QT&#47;QTc of the proband&#44; her father&#44; and her son were prolonged &#40;410&#47;482&#160;ms&#44; 461&#47;461&#160;ms&#44; 450&#47;483&#160;ms&#41;&#46; Schwartz&#39;s score was&#160;8&#44; 4&#44; 5&#46;5&#160;for the proband&#44; her father&#44; and her son&#46; According to the QTc and Schwartz score&#44; the proband and her father and son were clinically diagnosed as LQTS&#44; however&#44; the father and son were asymptomatic&#46;</p><elsevierMultimedia ident="fig0002"></elsevierMultimedia><elsevierMultimedia ident="fig0003"></elsevierMultimedia><elsevierMultimedia ident="tbl0001"></elsevierMultimedia></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0017">Lidocaine normalized the QTc in proband with LQTS</span><p id="para0019" class="elsevierStylePara elsevierViewall">Lidocaine tests showed QTc were reduced after lidocaine infusion in all time points&#46; QTc interval shortened by&#160;&#8805; 30&#160;ms from baseline&#160;482&#160;ms&#160;to&#160;450&#160;ms after the initial dose and to&#160;447&#160;ms 45&#160;minutes after the maintenance dose&#44; suggesting a positive response to lidocaine treatment&#46; Despite the QTc reductions in other time points being less than&#160;30&#160;ms&#44; the attenuations were very close to the positive diagnostic criteria &#40;Supplemental Fig&#46; 4 and <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#41;&#46;</p></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0018">Mutation detection and verification</span><p id="para0020" class="elsevierStylePara elsevierViewall">The variants with an allele frequency&#160;&#62; 5&#160;&#37; in the dbSNP database&#44; 1000&#160;human genome dataset&#44; Exome Aggregation Consortium &#40;ExAC&#41;&#44; and genome Aggregation Database &#40;gnomAD&#41; were excluded from the Next-generation sequencing data&#46; By using the filtering criteria and analyzing the pipeline described in the Methods&#44; a deletion-frameshift mutation&#44; KCNH2&#40;NM&#95;000238&#46;3&#41;&#58; c&#46;3099&#95;3112del&#44; in exon&#160;13 of KCNH2 gene was discovered in both the proband and her father&#46; The mutation was screened in genomic DNAs of all family members by Sanger sequencing&#46; However&#44; no mutation at this site was observed in other family members except the proband&#44; her father and son &#40;<a class="elsevierStyleCrossRef" href="#fig0004">Fig&#46; 4</a>&#41;&#46; This variant was first reported as a putative LQTS-associated mutation by Jamie in&#160;2009&#44;<a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> but nothing has been reported about relationship between the phenotype and genotype of this mutation&#46; This heterozygous mutation resides in the distal C-terminus of the Kv11&#46;1&#160;channel&#44; very close to the coiled-coil domain &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 5</a>&#41;&#44; and causes a frameshift mutation after the amino acid&#160;1033 &#40;Arginine&#41;&#44; which replaces the original&#160;126&#160;amino acids with&#160;78&#160;novel amino acids &#40;p&#46; Pro1034GlyfsTer80&#41;&#46;</p><elsevierMultimedia ident="fig0004"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019">Three years follow-up results</span><p id="para0021" class="elsevierStylePara elsevierViewall">In the ICD implantation procedure&#44; the right ventricle lead&#39;s pacing parameters were&#160;0&#46;5V &#40;threshold&#41;&#44; 10&#46;8&#160;mv &#40;R wave amplitude&#41; and 1000&#160;&#937; &#40;impedance&#41; while the right arial lead&#39;s pacing parameters were 0&#46;5V &#40;threshold&#41;&#44; 3&#46;1&#160;mv &#40;R wave amplitude&#41; and 740&#160;&#937; &#40;impedance&#41;&#46; The initial pacemaker&#39;s programming control set the pacing rate at&#160;80&#160;beats per minute&#44; and ATP function was turned on&#44; 3&#160;Burst&#44; 3&#160;Ramp&#44; and alternate&#59; defibrillation discharge energy was&#160;35J when ventricular tachycardia rate&#160;&#62; 180&#160;beats per minute or ventricular fibrillation&#160;&#62; 200&#160;beats per minute&#46; During the&#160;3-month follow-up&#44; the patient did not have any discomfort&#44; and the pacemaker&#39;s programing control recorded&#160;304&#160;episodes of non-sustained ventricular tachycardia &#40;&#62; 4&#160;beats&#44; &#62; 182&#160;bpm&#41;&#44; however&#44; no discharge was recorded&#46; After&#160;a 3-years follow-up&#44; no cardiac event occurred&#44; and the pacemaker&#39;s programming control recorded only&#160;47&#160;episodes of non-sustained ventricular tachycardia whilst no discharge was recorded since the first time follow-up&#46; 12-leads electrocardiogram showed that QTc was&#160;473&#160;ms without pacing and 459&#160;ms with pacing &#40;Supplemental Fig&#46; 5&#41;&#44; echocardiography is normal and the ambulatory Holter monitoring showed no ventricular tachycardia were recorded in&#160;24&#160;hours&#46;</p></span></span><span id="sec0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0020">Discussion</span><p id="para0022" class="elsevierStylePara elsevierViewall">15&#160;autosomal dominant genes have been found to be associated with LQT1-15&#160;subtypes&#44; including KCNQ1&#44; KCNH2&#44; SCN5A&#44; ANKB&#44; KCNE1&#44; KCNE2&#44; KCNJ2&#44; CACNA1C&#44; CAV3&#44; SCN4B&#44; AKAP9&#44; SNTA1&#44; KCNJ5&#44; CALM1&#44; CALM2&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a><a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> Among these mutations&#44; LQT1 &#40;KCNQ1&#41; and LQT2 &#40;KCNH2&#41; are the most common types of LQTS&#44; accounting for more than&#160;70&#160;&#160;&#37; of LQTS&#44; whilst LQT3 &#40;SCN5A&#41; is responsible for less than&#160;10&#160;&#37;&#160;of the cases&#46; Clinically&#44; cardiac events with LQT1 are usually triggered by exercise whilst a sudden startle or loud noise and emotional stress are potential triggers for LQT2&#44; and LQT3 usually have events at sleep&#46; On the surface electrocardiogram&#44; LQT1 manifests as a broad-based and symmetrical T-wave with a prolonged QTc interval&#59; LQT2 manifests as a bifid or notched T-wave that is asymmetrical and of low amplitude&#59; LQT3 may manifest as a prolonged isoelectric interval preceding a relatively normal T-wave morphology&#46; Although ECG and clinical features vary a great deal in various genotypes of the LQTS&#44; not every case fits these characteristics&#44; even the different members in the same pedigree have different T-wave morphologies&#46; Some studies have shown that in genotype-positive LQTS families&#44; the penetrance of pathogenic variants may be low for certain variants&#44; indicating that the contribution of common variants to disease susceptibility may also contribute to variable disease penetrance&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a><a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> On the other side&#44; the identification of a novel or an ambiguous variant of uncertain significance may rarely be clinically informative&#44; which increases the risk of misinterpretation of genetic test results and further leads to potentially harmful diagnosis miscues&#46; Along with the rapid development of genetic test technology&#44; extensive clinical research of the common or uncertain variants is essential to the distinction of true LQTS-causative mutations from background genetic noise&#44; finally&#44; leading much more accurate diagnosis and better therapeutic approaches&#46;</p><p id="para0023" class="elsevierStylePara elsevierViewall">Among the&#160;900&#160;mutations in the KCNH2 gene&#44; almost half of the suspected LQT2-causing mutations are missense mutations&#46; Functional studies suggest that about&#160;90&#160;&#37;&#160;of these mutations disrupt the intracellular transport or trafficking of the KCNH2-encoded Kv11&#46;1 channel protein to the cell surface membrane&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> In this study&#44; a Chinese Han family with a KCNH2 gene mutation is reported with the proband diagnosed as LQTS because of recurrent ventricular tachycardia and syncope with QTc of&#160;482-523ms&#46; Gene sequencing analyses and ECG examination of the whole family showed a deletion mutation KCNH2&#40;NM&#95;000238&#46;3&#41;&#58;c&#46;3099&#95;3112del for the proband&#44; her father&#44; and son&#46; All of these three members exhibited prolonged QT intervals fit for the LQTS diagnosis criteria&#44; whereas other family members without the mutation showed normal QT intervals&#46; The proband&#39;s sister&#44; who fortunately did not inherit this mutation from her father&#44; showed normal QT interval without symptoms compared with the proband&#44; indicating that this mutation may be a pathogenic mutation of KCNH2&#46; This mutation was first reported by Jamie <a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> in&#160;2009 as a putative LQTS-associated variant by genetic test in&#160;2500 cases cohort&#46; However&#44; there is a lack of detailed clinical manifestations described and functional investigations of this mutation conducted&#46; The present report is the first to discover the genetic link of this mutation with LQTS in detailed clinical evidence&#46;<a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> The mutation p&#46;Pro1034GlyfsTer80 we reported is in exon&#160;13 of the KCNH2 gene and the region of the distal COOH terminus &#40;residues&#160;1018&#8211;1122&#41;&#46; Residues&#160;1036&#8210;1074 is a conserved coiled-coil domain named TTC or CCD&#44; which is thought to be essential for subunit assembly&#47;tetramerization&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> The mutation is just&#160;3&#160;amino acids preceding the TTC domain and causes a frame-shift translation of TTC&#44; suggesting that amino acid changes in TTC region of Kv11&#46;1 channel protein may cause QT prolongation and adverse clinical outcomes&#44; supporting a novel functional role of TTC region in the normal physiology of KCNH2 channel&#46;</p><p id="para0024" class="elsevierStylePara elsevierViewall">Clinical data of the family show that this variant is not a putative mutation but a pathogenic mutation&#44; especially for female individuals&#46; Lidocaine attenuation testing of the proband with a positive response provides additional insight into the predictive value of this test&#46; The patient was prescribed propranolol and mexiletine because beta blockers are regarded as first-line therapy for LQTS&#44; but current standard therapies may not fully protect patients from occurrence of cardiac arrhythmias&#46; ICD is another treatment proving effective in treating arrhythmia and preventing sudden death&#46;<a class="elsevierStyleCrossRefs" href="#bib0016"><span class="elsevierStyleSup">16&#8211;18</span></a> After ICD implantation and follow-up for&#160;3 years&#44; non-sustained ventricular tachycardias are reduced from&#160;304&#160;episodes at the&#160;3-months&#8217; visit to&#160;47&#160;episodes at the third year&#39;s visit&#44; and the QTc intervals are nearly normal &#40;459&#160;ms&#41; with pacing at&#160;80&#160;beats&#47;min&#46; Moreover&#44; the patient did not show any symptoms again during the follow-up&#46; The present study along with others suggests that for patients with LQTS&#44; therapeutic decisions should be made based on QTc&#44; the presence of clinical and electrocardiographic features&#44; and the confirmed pathogenic variant detected by genetic test&#46;</p><p id="para0025" class="elsevierStylePara elsevierViewall">Gender differences in congenital LQTS are well established in clinics&#44; but the underlying causes remain to be determined&#46; The follow-up study of a large congenital LQTS population of&#160;1710&#160;patients during a median of&#160;71&#160;years indicates that the female sex is an independent predictor of life-threatening events &#40;HR&#160;&#61;&#160;1&#46;70&#59; 95&#160;&#37;&#160;CI&#160;1&#46;00&#160;to&#160;2&#46;88&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;048&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> In this&#44;genotype-positive LQTS family&#44; the seizure of clinical symptoms is also in a sex-specific predilection in women&#46; The female proband suffered recurrent life-threatening ventricular arrhythmias arrhythmias and syncope&#44; but the two male variant carriers did not show any symptoms and arrhythmia in daily life or routine health examinations&#44; even though they also have prolonged QTc intervals and typical T-wave morphology in ECG&#44; which could be due to the different androgen levels between the two genders&#46; Interestingly&#44; the morphology of T-wave differs slightly between males and females in this family&#44; the female proband has a flat bifid T-wave in electrocardiogram which could lead to missed diagnosis&#44; whereas the two male carriers have the typical LQT2 T-wave with clear notches&#46; Publish data show that LQT2 males with pore location mutations have a significantly higher risk of cardiac events than non-pore location males &#40;HR&#61;6&#46;01&#59; 95&#160;&#37;&#160;CI&#160;1&#46;50&#8211;24&#46;08&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;011&#41; whereas this association is not found in females&#46;<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> In the family of this study&#44; the mutation is not in the pore formation location&#44; which may explain why the two male carriers do not experience any arrhythmia attack although QTc intervals fit for the diagnosis criteria&#46; As sex hormones have varying effects on the potassium currents in both genomic- and non-genomic-regulated pathways <a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a>&#44; further proteomics studies are needed to explain whether different mutations in Kv11 exhibit different reactions to estrogen&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0021">Conclusion</span><p id="para0026" class="elsevierStylePara elsevierViewall">In this study&#44; the authors confirmed a putative mutation KCNH2&#40;NM&#95;000238&#46;3&#41;&#58; c&#46;3099&#95;3112del as a potential pathogenic mutation&#46; The clinical feature of this mutation is described for the first time&#46; The family pedigree information revealed a gender difference with this mutation in clinical features and T-wave morphology&#46; The female proband also showed a positive reaction to lidocaine attenuation test&#46; The patient was treated by propranolol&#44; mexiletine and ICD implantation&#44; and no sustained ventricular tachycardia&#44; ventricular fibrillation or syncope were observed in a&#160;3-year follow-up monitoring&#46;</p></span><span id="sec0016" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0022">Authors&#8217; contributions</span><p id="para0028" class="elsevierStylePara elsevierViewall">ZunPing Ke responsible for data curtion and software&#44; Chao Li and Gang Bai responsible for investigation&#44; Li Tan&#44; JunFeng Wang and Ming Zhou responsible for project administration&#44; JianHua Zhou responsible for visualization&#44; Xiao Dong responsible for writing original draft&#44; funding acquisition and supervision&#44; Shi-You Chen responsible for writing review &#38; editing&#46;</p></span><span id="sec0017" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0023">IRB Information</span><p id="para0029" class="elsevierStylePara elsevierViewall">The present study was approved by the Medical Ethics Committee of Shiyan Taihe Hospital&#46; Reference number&#58;&#160;2019-34&#46;</p><p id="para0030" class="elsevierStylePara elsevierViewall">This observational study conforms to specific study guidelines of STROBE statement&#46;</p></span></span>"
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              "titulo" => "Lidocaine attenuation testing"
            ]
            3 => array:2 [
              "identificador" => "sec0006"
              "titulo" => "Next-generation sequencing &#40;NGS&#41; and sanger sequencing"
            ]
            4 => array:2 [
              "identificador" => "sec0007"
              "titulo" => "ICD implantation"
            ]
            5 => array:2 [
              "identificador" => "sec0008"
              "titulo" => "Follow up"
            ]
          ]
        ]
        5 => array:3 [
          "identificador" => "sec0009"
          "titulo" => "Results"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0010"
              "titulo" => "Clinical abnormality of patients with LQTS"
            ]
            1 => array:2 [
              "identificador" => "sec0011"
              "titulo" => "Lidocaine normalized the QTc in proband with LQTS"
            ]
            2 => array:2 [
              "identificador" => "sec0012"
              "titulo" => "Mutation detection and verification"
            ]
            3 => array:2 [
              "identificador" => "sec0013"
              "titulo" => "Three years follow-up results"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0014"
          "titulo" => "Discussion"
        ]
        7 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Conclusion"
        ]
        8 => array:2 [
          "identificador" => "sec0016"
          "titulo" => "Authors&#8217; contributions"
        ]
        9 => array:2 [
          "identificador" => "sec0017"
          "titulo" => "IRB Information"
        ]
        10 => array:2 [
          "identificador" => "xack769885"
          "titulo" => "Acknowledgments"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2023-03-03"
    "fechaAceptado" => "2023-09-04"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1869172"
          "palabras" => array:5 [
            0 => "LQTs"
            1 => "KCNH2"
            2 => "Kv11&#46;1"
            3 => "Ventricular arrhythmias"
            4 => "Ventricular fibrillation"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "highlights" => array:2 [
      "titulo" => "Highlights"
      "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><p id="spara007" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">&#8226;</span><p id="para0001" class="elsevierStylePara elsevierViewall">A mutation reported in this article appeared to be a definite pathogenic mutation of LQT2&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0002"><span class="elsevierStyleLabel">&#8226;</span><p id="para0002" class="elsevierStylePara elsevierViewall">This mutation exhibit gender differences in clinical symptoms and T-wave morphology&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0002a"><span class="elsevierStyleLabel">&#8226;</span><p id="para0002a" class="elsevierStylePara elsevierViewall">The female proband with this mutation showed a positive reaction to lidocaine attenuation test&#46;</p></li></ul></p></span>"
    ]
    "resumen" => array:1 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Introduction</span><p id="spara008" class="elsevierStyleSimplePara elsevierViewall">Long QT Syndrome &#40;LQTS&#41; is an inherited disease with an abnormal electrical conduction system in the heart that can cause sudden death as a result of QT prolongation&#46; LQT2 is the second most common subtype of LQTS caused by loss of function mutations in the potassium voltage-gated channel subfamily H member&#160;2 &#40;KCNH2&#41; gene&#46; Although more than&#160;900&#160;mutations are associated with the LQTS&#44; many of these mutations are not validated or characterized&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Methods and results</span><p id="spara009" class="elsevierStyleSimplePara elsevierViewall">Sequencing analyses of genomic DNA of a family with LQT2 identified a putative mutation&#46; i&#46;e&#46;&#44; KCNH2&#40;NM&#95;000238&#46;3&#41;&#58; c&#46;3099&#95;3112del&#44; in KCNH2 gene which appeared to be a definite pathogenic mutation&#46; The family pedigree information showed a gender difference in clinical features and T-wave morphology between male and female patients&#46; The female with mutation exhibited recurring ventricular arrhythmia and syncope&#44; while two male carriers did not show any symptoms&#46; In addition&#44; T-wave in females was much flatter than in males&#46; The female proband showed a positive reaction to the lidocaine test&#46; Lidocaine injection almost completely blocked ventricular arrhythmia and shortened the QT interval by&#160;&#8805;30&#160;ms&#46; Treatment with propranolol&#44; mexiletine&#44; and implantation of cardioverter-defibrillators prevented the sustained ventricular tachycardia&#44; ventricular fibrillation&#44; and syncope&#44; as assessed by a 3-year follow-up evaluation&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Conclusions</span><p id="spara010" class="elsevierStyleSimplePara elsevierViewall">A putative mutation c&#46;3099&#95;3112del in the KCNH2 gene causes LQT2 syndrome&#44; and the pathogenic mutation mainly causes symptoms in female progeny&#46;</p></span>"
        "secciones" => array:3 [
          0 => array:2 [
            "identificador" => "abss0002"
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          1 => array:2 [
            "identificador" => "abss0003"
            "titulo" => "Methods and results"
          ]
          2 => array:2 [
            "identificador" => "abss0004"
            "titulo" => "Conclusions"
          ]
        ]
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="para0027a" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="ecom0001"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix"
            "titulo" => "Supplementary materials"
            "identificador" => "sec0019"
          ]
        ]
      ]
    ]
    "multimedia" => array:7 [
      0 => array:8 [
        "identificador" => "fig0001"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1286
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          0 => array:3 [
            "identificador" => "alt0001"
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            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Pedigree of the family with long QT syndrome&#46; I&#44; II&#44; III&#44; and IV refer to the first&#44; second&#44; third&#44; and fourth generations of the family&#44; respectively&#46; Black represents clinically diagnosed patients with Long QT syndrome&#44; shadows represent carriers of pathogenic mutations&#44; and the arrow indicates the proband&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "fig0002"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1419
            "Ancho" => 3333
            "Tamanyo" => 622390
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          0 => array:3 [
            "identificador" => "alt0002"
            "detalle" => "Fig "
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">24h-ambulatory Holter monitoring recorded frequent ventricular premature beats&#44; recurrent ventricular tachycardia&#44; and fibrillation of the proband&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "fig0003"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1543
            "Ancho" => 1667
            "Tamanyo" => 381150
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0003"
            "detalle" => "Fig "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">ECG of the proband and family members in V5 or V3 lead&#46; Different T-wave morphologies were observed&#46; Individuals with clinical diagnosed long QT2 syndrome including the proband &#40;III-2&#41;&#44; and her farther &#40;II-2&#41; and her son &#40;IV-1&#41; showed bifid or notched T-wave in ECG&#44; pointed by red arrow&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "fig0004"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 4281
            "Ancho" => 3333
            "Tamanyo" => 1147697
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0004"
            "detalle" => "Fig "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara004" class="elsevierStyleSimplePara elsevierViewall">Sanger sequencing showed a heterozygous deletion-frameshift mutation&#44; KCNH2&#40;NM&#95;000238&#46;3&#41;&#58;c&#46;3099&#95;3112del in KCNH2 gene in the proband&#44; her father and her son&#44; whereas other family members are normal&#46; Red brackets indicate the frameshifted DNA sequence after deletion&#59; green brackets show the original DNA sequence in individuals without mutation&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 1528
            "Ancho" => 1667
            "Tamanyo" => 228765
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        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0005"
            "detalle" => "Fig "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara005" class="elsevierStyleSimplePara elsevierViewall">A structural model of the &#945;-subunit of Kv11&#46;1 protein and location of the mutation p&#46;Pro1034GlyfsTer80 described in this family&#46; Red star represents the mutation p&#46;Pro1034GlyfsTer80&#44; S1&#8210;S6 is the transmembrane domains of Kv11&#46;1&#59; PAS is the Per-Arnt-Sim domain&#44; &#40;residues&#160;26&#8210;75&#41;&#59; C-linker &#40;residues&#160;667&#8210;744&#41;&#59; CNBHD is the cyclic nucleotide-binding homology domain &#40;residues&#160;748&#8210;865&#41;&#59; RXR is the ER retention signal &#40;residues&#160;1005&#8210;1007&#41;&#59; CCD is the coiled-coil domain &#40;residues&#160;1036&#8210;1074&#41;&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0001"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0006"
            "detalle" => "Table "
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          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">Subject</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">Sex</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0003"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">Age &#40;y&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">Heart rate &#40;bpm&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0005"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">PR interval &#40;ms&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0006"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">QRS duration &#40;ms&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0007"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">QT&#47;QTs &#40;ms&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0008"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">ECG characteristics</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0009"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">Clinical symtoms</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0010"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">Schwart score</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0011"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Father&#44; II-2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0013"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">123&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">461&#47;461&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Prolonged QT subtle notched T-wave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Mother&#44; II-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">101&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0025"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">190&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">330&#47;434&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Depressed ST segment flat T-wave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0029"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0031"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Proband&#44; III-2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">110&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">410&#47;482&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Short PR interval prolonged QT bifid T-wave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Syncope&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Sister&#44; III-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">316&#47;385&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Normal ECG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Son&#44; IV-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">103&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">450&#47;483&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Short PR interval prolonged QT notched T-wave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0061"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Uncle&#44; II-3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0065"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">146&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">346&#47;402&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Normal ECG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0069"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0071"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Uncle&#44; II-4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">136&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">349&#47;401&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Normal ECG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0081"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Uncle&#44; II-5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0085"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">153&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">365&#47;419&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Normal ECG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spara006" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of family members in a Chinese Han family with LQTS&#46; QT intervals were measured by Tangent method from lead&#160;II or lead&#160;V5 as a mean of&#160;3&#160;consecutive beats&#46; QTc were calculated by Bazett correction formula&#46;</p>"
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                      "titulo" => "Impact of genetics on the clinical management of channelopathies"
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                            5 => "S Shen"
                          ]
                        ]
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                      "doi" => "10.1007/s00246-019-02151-x"
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                          ]
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                        "tituloSerie" => "Br J Sports Med"
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                            0 => "AS Vink"
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                            3 => "JM Meskill"
                            4 => "D Ye"
                            5 => "MJ&#46; Ackerman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.hrthm.2017.04.020"
                      "Revista" => array:7 [
                        "tituloSerie" => "Heart Rhythm"
                        "fecha" => "2017"
                        "volumen" => "14"
                        "numero" => "8"
                        "paginaInicial" => "1173"
                        "paginaFinal" => "1179"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28412158"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0009"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Spectrum and prevalence of mutations from the first 2&#44;500 consecutive unrelated patients referred for the FAMILION&#174; long QT syndrome genetic test"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "JD Kapplinger"
                            1 => "DJ Tester"
                            2 => "BA Salisbury"
                            3 => "JL Carr"
                            4 => "C Harris-Kerr"
                            5 => "GD Pollevick"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.hrthm.2009.05.021"
                      "Revista" => array:7 [
                        "tituloSerie" => "Heart Rhythm"
                        "fecha" => "2009"
                        "volumen" => "6"
                        "numero" => "9"
                        "paginaInicial" => "1297"
                        "paginaFinal" => "1303"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19716085"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The genetic architecture of long QT syndrome&#58; a critical reappraisal"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "JR Giudicessi"
                            1 => "AAM Wilde"
                            2 => "MJ&#46; Ackerman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.tcm.2018.03.003"
                      "Revista" => array:7 [
                        "tituloSerie" => "Trends Cardiovasc Med"
                        "fecha" => "2018"
                        "volumen" => "28"
                        "numero" => "7"
                        "paginaInicial" => "453"
                        "paginaFinal" => "464"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29661707"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0011"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interplay between genetic substrate&#44; QTc duration&#44; and arrhythmia risk in patients with long QT syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A Mazzanti"
                            1 => "R Maragna"
                            2 => "G Vacanti"
                            3 => "N Monteforte"
                            4 => "R Bloise"
                            5 => "M Marino"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2018.01.078"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2018"
                        "volumen" => "71"
                        "numero" => "15"
                        "paginaInicial" => "1663"
                        "paginaFinal" => "1671"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29650123"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0012"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Transethnic genome-wide association study provides insights in the genetic architecture and heritability of long QT syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N Lahrouchi"
                            1 => "R Tadros"
                            2 => "L Crotti"
                            3 => "Y Mizusawa"
                            4 => "PG Postema"
                            5 => "L Beekman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.120.045956"
                      "Revista" => array:7 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2020"
                        "volumen" => "142"
                        "numero" => "4"
                        "paginaInicial" => "324"
                        "paginaFinal" => "338"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32429735"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0013"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long QT syndrome type 2&#58; emerging strategies for correcting class 2 KCNH2 &#40;hERG&#41; mutations and identifying new patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M Ono"
                            1 => "DE Burgess"
                            2 => "EA Schroder"
                            3 => "CS Elayi"
                            4 => "CL Anderson"
                            5 => "CT January"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3390/biom10081144"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biomolecules"
                        "fecha" => "2020"
                        "volumen" => "10"
                        "numero" => "8"
                        "paginaInicial" => "1144"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32759882"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0014"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Targeted next generation sequencing revealed a novel deletion-frameshift mutation of KCNH2 gene in a Chinese Han family with long QT syndrome&#58; a case report and review of Chinese cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F Du"
                            1 => "G Wang"
                            2 => "D Wang"
                            3 => "G Su"
                            4 => "G Yao"
                            5 => "W Zhang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MD.0000000000019749"
                      "Revista" => array:6 [
                        "tituloSerie" => "Medicine"
                        "fecha" => "2020"
                        "volumen" => "99"
                        "numero" => "16"
                        "paginaInicial" => "e19749"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32311972"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Functional study of a KCNH2 mutant&#58; Novel insights on the pathogenesis of the LQT2 syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R De Zio"
                            1 => "A Gerbino"
                            2 => "C Forleo"
                            3 => "M Pepe"
                            4 => "S Milano"
                            5 => "S Favale"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jcmm.14521"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Cell Mol Med"
                        "fecha" => "2019"
                        "volumen" => "23"
                        "numero" => "9"
                        "paginaInicial" => "6331"
                        "paginaFinal" => "6342"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31361068"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0016"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The efficacy of beta-blockers in patients with long QT syndrome 1-3 according to individuals&#39; gender&#44; age&#44; and qtc intervals&#58; a network meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L Han"
                            1 => "F Liu"
                            2 => "Q Li"
                            3 => "T Qing"
                            4 => "Z Zhai"
                            5 => "Z Xia"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Front Pharmacol"
                        "fecha" => "2020"
                        "volumen" => "11"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0017"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical aspects of the three major genetic forms of long QT syndrome &#40;LQT1&#44; LQT2&#44; LQT3&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V Kutyifa"
                            1 => "UA Daimee"
                            2 => "S McNitt"
                            3 => "B Polonsky"
                            4 => "C Lowenstein"
                            5 => "K Cutter"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/anec.12537"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Noninvasive Electrocardiol"
                        "fecha" => "2018"
                        "volumen" => "23"
                        "numero" => "3"
                        "paginaInicial" => "e12537"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29504689"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0018"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Independent validation and clinical implications of the risk prediction model for long QT syndrome &#40;1-2-3-LQTS-Risk&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A Mazzanti"
                            1 => "A Trancuccio"
                            2 => "D Kukavica"
                            3 => "E Pagan"
                            4 => "M Wang"
                            5 => "M Mohsin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/europace/euab238"
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                        "tituloSerie" => "Europace"
                        "fecha" => "2022"
                        "volumen" => "24"
                        "numero" => "4"
                        "paginaInicial" => "614"
                        "paginaFinal" => "619"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34505884"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0019"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk stratification of type 2 long QT syndrome mutation carriers with normal QTC interval&#58; the value of gender&#44; T-wave morphology and mutation type"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "PG Platonov"
                            1 => "S McNitt"
                            2 => "B Polonsky"
                            3 => "SZ Rosero"
                            4 => "V Kutyifa"
                            5 => "A Huang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Circ Arrhythm Electrophysiol"
                        "fecha" => "2018"
                        "volumen" => "11"
                        "numero" => "7"
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                  ]
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              ]
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                      "titulo" => "Sexual dimorphisms&#44; anti-hormonal therapy and cardiac arrhythmias"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V Grouthier"
                            1 => "MYY Moey"
                            2 => "E Gandjbakhch"
                            3 => "X Waintraub"
                            4 => "C Funck-Brentano"
                            5 => "A Bachelot"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3390/ijms22031464"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Mol Sci"
                        "fecha" => "2021"
                        "volumen" => "22"
                        "numero" => "3"
                        "paginaInicial" => "1464"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33540539"
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        "texto" => "<p id="para0032" class="elsevierStylePara elsevierViewall">The research is supported by <span class="elsevierStyleGrantSponsor" id="gs0001">Natural Science Foundation of Hubei Province of China</span>&#58; The role of <span class="elsevierStyleGrantSponsor" id="gs0002">MYBPC3 frameshift mutation in hypertrophic cardiomyopathy</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0001">2022CFB436</span>&#41;&#59; Joint Fund of <span class="elsevierStyleGrantSponsor" id="gs0003">Taihe hospital and BIOTECAN for Precision Medicine&#58; The genotype classification and efficiency of PCI procedure in HCM patients with coronary artery disease</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0003">2016JZ09</span>&#41;&#59; <span class="elsevierStyleGrantSponsor" id="gs0004">Guiding Project of Hubei Provincial Department of Education of China</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0004">B2016116</span>&#41;&#46;</p>"
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ISSN: 18075932
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