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"documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Clin. 2018;150:209-14" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Avoidable hospitalizations due to adverse drug reactions in an acute geriatric unit. Analysis of 3,292 patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "209" "paginaFinal" => "214" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hospitalizaciones evitables por reacciones adversas a medicamentos en una unidad geriátrica de agudos. 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The overall prevalence of hereditary neuropathies is estimated at 30:100,000 population. More than half of these cases are CMT type 1. CMTX1 is the second most common type of CMT representing in at least 10–20% of cases with CMT neuropathy.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">This X-linked dominant type of CMT is due to mutations in the gap junction protein-β1 (GJB1) or connexin 32 (Cx32) genes located on chromosome Xq13.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">CMTX1 is characterized by moderate to severe motor and sensory neuropathy with earlier onset in affected males, and usually mild to no symptoms in carrier females. The milder phenotype of CMTX1 in females can be caused by random chromosome X inactivation (lyonization).<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">4,5</span></a> Symptoms typically develop after the age of twenty years in females, and the onset is usually within the first decade in males.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Preimplantation genetic diagnosis (PGD) is an option for reproductive-age couples who have a genetic burden of CMTX1. Currently, several PGD cases of CMTX1 have been reported. We performed PGD using an indirect linkage analysis in a female proband with a heterozygous variant p.Leu9Phe (c.27G¿T, reference sequence #NM_000166.5) reported in Brozkova et al.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> and showed that CMTX1 was also observed in her mother, sister, two uncles and grandmother.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">This clinical study was conducted from January, 2010 to December, 2014 in the Centre for Medical Genetics and Reproductive Medicine Gennet in Prague. This study conformed to the principles of the Declaration of Helsinki. It was approved by the Ethics committee of Gennet, Prague, Czech Republic.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The proband introduced her family history in some family members with CMTX1 symptoms with later onset and milder progression in females than males. Proband's mother had first suspicion for CMTX1 at her age of 19 years but severe neurological problems in her began from the age of 35 years (Electromyography (EMG) examination proved significantly slowed motor nerve conduction velocity in legs and arms but without atrophy.) while her mother (proband's grandmother) suffered gait problems in older age. Onset of hereditary motor and sensory neuropathy (HMSN) started in two proband's uncles, when they were 10 and 15 years old, and CMTX1 progressed to arm and leg weakness and atrophy. Proband and her twin sister diagnosed with CMTX1 have only milder leg defects (e.g. calf crams) without atrophy. The pedigree of investigated family with affected members is showed in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Totally, we examined twelve samples. Within preparing of PGH panel, we used to four samples of genomic DNA from peripheral blood (female proband, her uncle and mother, male partner) and within in vitro fertilization (IVF) cycle further four samples of DNA from embryos, numbered 1–4. Four months after PGD cycle, amniotic fluid sampling from pregnant proband was used to verification of embryo status of carrying two low-risk haplotypes. Screening criteria in embryos are based on carrying low- and high-risk haplotype heterozygozity, valid only for females in X-linked recessive diseases. In X-linked dominant diseases, as in case of CMTX1, embryos with high-risk haplotype should be excluded. In year 2014, the reproductive couple returned for an examination of spontaneous gravidity. We tested three samples of chorionic villi, whereof two samples were used to cytogenetic analysis; and one sample with maternal genomic DNA were used to quantitative fluorescent PCR (QF-PCR).</p><p id="par0040" class="elsevierStylePara elsevierViewall">The reproductive couple and their relatives provided written informed consent for participating in all PGD cycle.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Pre-case haplotyping analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">The pre-case haplotyping (PGH) protocol was performed with reproductive couple, who was trying to conceive, with the proband's mother and one of her uncles. Genomic DNA was extracted from the peripheral blood using a standard protocol (QIAamp DNA blood Mini kit, Qiagen, Hilden, Germany; Supplier: Dynex, Buštěhrad, Czech Republic).</p><p id="par0050" class="elsevierStylePara elsevierViewall">We designed eight short tandem repeat (STR) markers in front of the <span class="elsevierStyleItalic">GJB1</span> gene (DXS8040, DXS1216, DXS8111, DXS1275, DXS8031, DXS983, DXS8107 and DXS8052), eight STR markers behind the <span class="elsevierStyleItalic">GJB1</span> gene (DXS8101, DXS8046, DXS8070, DXS8079, DXS8060, DXS8092, DXS8037 and DXS1221) and two intragenic STR markers (21xTG and 11xTTTA).</p><p id="par0055" class="elsevierStylePara elsevierViewall">Polymerase chain reaction (PCR) assay using fluorescently labelled primers were performed as two sets (A/B) for the PGH panel. Each set included some of the STR markers located behind and in front of the <span class="elsevierStyleItalic">GJB1</span> gene. The universal STR markers AMELX/Y and SRY were incorporated in the sets to confirm the female or male sex.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">IVF protocol</span><p id="par0060" class="elsevierStylePara elsevierViewall">PGD requires in vitro fertilization (IVF) and control of the processes of oocyte maturation, fertilization and implantation, to select only healthy embryos for transfer back to the uterus.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Single cells (blastomeres) were biopsied from particular cleavage-stage embryos [numbered 1–4] on day 3 of the IVF cycle. The blastomeres were washed in a special solution, lysed and then used directly for multiple displacement amplification (MDA) as described by Renwick et al.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The MDA products were subsequently subjected to PCR assays using the fluorescent STR markers to identify embryos with high- and low-risk haplotypes according to the PGH panel. In X-linked dominant diseases, healthy embryos are routinely transferred on day 5, and affected embryos with the high-risk haplotype are excluded.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Other analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">The prenatal diagnosis of spontaneous gravidity consisted of an analysis of the chorionic villi by quantitative fluorescent PCR (QF-PCR) to detect aneuploidy of chromosomes 13, 18, 21, X and Y. The karyotype of foetus was established by the Giemsa banding method.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">Before commencing the PGD procedure, the reproductive-age couple was consulted by a clinical geneticist regarding the possible risks of PGD and risks of a spontaneous gravidity with CMTX1 for male and female sex. The female proband introduced her medical history in which CMTX1 was manifested in her mother, sister, both uncles and grandmother. She was confirmed to have a heterozygous pathogenic mutation c.27G¿T in the <span class="elsevierStyleItalic">GJB1</span> gene at 17 years of age.</p><p id="par0085" class="elsevierStylePara elsevierViewall">To initiate the PGD analysis for X-linked monogenic disorders, it was necessary to establish the p.Leu9Phe mutation in the <span class="elsevierStyleItalic">GJB1</span> gene (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Based on the determination of specific causal mutation, we could design primers for the STR markers (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), prepare the specific PGH panel, and identify the mutated/high-risk haplotypes obtained from the biological material of the family members (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Then, the couple underwent two IVF protocols. The first PGD cycle of CMTX1 was cancelled during ovarian stimulation because the female proband displayed a minimal reaction to the hormone dose.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In the last PGD cycle, the female proband had twelve punctured follicles, ten of which gained oocytes. Based on oocyte development, only four oocytes were fertilized by intracytoplasmic sperm injection (ICSI).</p><p id="par0100" class="elsevierStylePara elsevierViewall">On day 3, four cleavage-stage embryos {1, 2, 3 and 4} were biopsied for the haplotyping analysis. Initially, the DNA of single blastomeres was amplified successfully by MDA. The MDA products were subsequently subjected to STR analysis for comparison with the extracted DNA from both partners. The embryos were determined to be healthy because they carried the low-risk haplotype. Three embryos {1, 3, and 4} were assessed as having the maternal low-risk haplotype of chromosome X and paternal haplotype of chromosome Y. Amplification was not detected in one embryo {2}. Therefore, we indicated that three male embryos were healthy, and two embryos {3 and 4} were transferred on the fifth day of the PGD cycle. Two embryos {1 and 2} embodied abnormal development, and therefore, we did not re-analyze the trophectoderm.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Three years later, the reproductive-age couple returned for an examination of spontaneous gravidity. A chorionic villus sample was tested for chromosomal abnormality by QF-PCR and cytogenetic analysis. Using QF-PCR, we determined that there was no aneuploidy of chromosomes 13, 18, 21, X and Y, and we established the female sex of the foetus. A comparison of the DNA profiles from the foetus and mother excluded maternal contamination in the chorionic villus samples.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Simultaneously, two samples of the chorionic villi were cultivated for cytogenetic analysis. Cytogenetic analysis confirmed the female sex of the foetus, and also identified a chromosomal aberration in one sample. Approximately 70% of the examined cells had pericentric inversion of chromosome 5 with a karyotype 46,XX,inv(5)(p15q12). A normal karyotype was detected in all cells of a second sample.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The parents did not want to terminate the pregnancy and further to determine the CMTX1 haplotypes in this foetus based on female proband's experience with CMTX1 and milder symptoms proven in affected female family members.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">PGD is a reproductive option for couples at substantial risk of conceiving a child affected with a non-lethal disorder as CMTX1 and who wish to avoid the emotional burden associated with an affected child, the termination of a pregnancy or recurrent miscarriages.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Many assisted reproduction centres offer PGD of CMTX1 for heterozygous females using in situ hybridization (FISH) to achieve an unaffected pregnancy. However, all male embryos are discarded in this process and it is not able to distinguish a heterozygous or healthy embryo with CMTX1. In contrast, PGD using haplotyping analysis may identify the haplotype status of affected/healthy male or carrier/healthy female embryos with recessive disorders and affected/healthy female embryos with dominantly inherited diseases. Within the last PGD cycle, we determined that three male embryos had the maternal low-risk haplotype of chromosome X (without mutation c.27G¿T), and thus the number of embryos recommended for possible transfer was increased.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Using indirect linkage analysis, PGD is based on whole genome amplification (WGA) through the MDA process and subsequent STR analysis. MDA, as well as the other WGA method, has the disadvantage of allelic dropout (ADO), which can lead to a misdiagnosis of embryo status. We only detected ADO in one analyzed embryo,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> where no DNA was amplified. It may have been caused by ADO of all of the examined alleles, the damage or absence of nuclear DNA in the blastomere, or chromosomal nullisomy.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> In the case of ambiguous results, we repeat entire process with trophectoderm on day 4 for an embryo to be transferred on day 5. We did not perform this second analysis of the trophectoderm for this embryo, because it exhibited abnormal embryonic development.</p><p id="par0135" class="elsevierStylePara elsevierViewall">CMTX1 is characterized by latest onset and milder symptoms in females than in males, in whom it produces serious defects. The milder phenotype of CMTX1, such as in our female proband, is probably caused by the inactivation of chromosome X (lyonization). Lyonization is a random process in embryonic development, and it cannot predict which chromosomes X will be silenced.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> Basically, this process is mosaic form of an inactivated and an activated chromosome X with various dosages in different tissues.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">12,13</span></a> Hemizygous males have only one chromosome Y and one chromosome X that will be equally expressed in all tissues. Hence, in a heterozygous female with CMTX1, the manifestation of the mutated <span class="elsevierStyleItalic">GJB1</span> gene on one chromosome X will compensated for by the transcription of the healthy <span class="elsevierStyleItalic">GJB1</span> gene on the second chromosome X in various proportions in different tissues.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Three years after the PGD cycle, the female proband became pregnant spontaneously. With the help of QF-PCR and the Giemsa banding method, the female sex of the foetus was determined. Based on the milder CMTX1 phenotype in the female proband, reproductive-age couple did not want to examine the haplotype status of CMTX1 in the <span class="elsevierStyleItalic">GJB1</span> gene in the foetus. However, the karyotype analysis of the chorionic villi detected a pericentric inversion of chromosome 5 in 70% of the examined cells in one sample, while a normal karyotype was detected in all cells of the second sample. This result could rise during embryo development where blastocyst cells divide into inner cell mass (ICM) and trophoblast (trophectoderm, TE). ICM gives rise to the embryo and proliferating cellular trophoblast forms chorionic villi which do not affect single embryo development. During chorionic villi biopsy, TE cells could be separated into two cultures with mosaicism (a part of cell population carrying a chromosome 5 pericentric inversion) and without mosaicism. Subsequently, TE cells could manifest to mosaic result in one cell culture. Another explanation of the accidental result of the mosaic pericentric inversion in the cells of the first sample would be a cultivated artefact. Provided that a mosaic form of this balanced structural aberration would be present in the foetus, the clinical consequence is not significant in childhood, but it can cause problems with infertility in the future.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">14,15</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">In our study, PGD helped a reproductive-age couple to have a healthy male gravidity. We recommend that this result is verified by amniotic fluid sampling, because it is impractical to detect mosaicism from single cells within a PGD cycle. Thus, mosaicism was excluded in the foetus after the PGD cycle.</p><p id="par0150" class="elsevierStylePara elsevierViewall">Generally, monogenic diseases in embryos can be detected by direct or indirect linkage analysis. We used the indirect linkage analysis because it has the advantage identifying possible aberrations in the examined chromosomes. Another benefit of the indirect linkage analysis is that the designed STR markers from one PGH panel of X-linked monogenic disease can be used for all families, even when there are a variety of pathogenic mutations in a single gene.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflict of interest</span><p id="par0155" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1009874" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec969293" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1009875" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec969292" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Pre-case haplotyping analysis" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "IVF protocol" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Other analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interest" ] 9 => array:2 [ "identificador" => "xack340684" "titulo" => "Acknowledgement" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-01-09" "fechaAceptado" => "2017-06-15" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec969293" "palabras" => array:4 [ 0 => "Indirect linkage analysis" 1 => "Haplotyping" 2 => "X-linked Charcot-Marie-Tooth disease" 3 => "X-chromosome inactivation" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec969292" "palabras" => array:4 [ 0 => "Análisis de ligamiento indirecto" 1 => "Haplotipificación" 2 => "Enfermedad de Charcot-Marie-Tooth ligada al cromosoma X" 3 => "Inactivación del cromosoma X" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To present methodical approach of preimplantation genetic diagnosis (PGD) as an option for an unaffected pregnancy in reproductive-age couples who have a genetic risk of the X-linked dominant peripheral neuropathy Charcot-Marie-Tooth type 1 disease.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We performed PGD of X-linked Charcot-Marie-Tooth type 1 disease using haplotyping/indirect linkage analysis, when during analysis we reach to exclude embryos that carry a high-risk haplotype linked to the causal mutation p.Leu9Phe in the <span class="elsevierStyleItalic">GJB1</span> gene.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Within the PGD cycle, we examined 4 blastomeres biopsied from cleavage-stage embryos and recommended 3 embryos for transfer. Two embryos were implanted into the uterus; however, it resulted in a singleton pregnancy with a male descendant. Three years later, the couple returned again with spontaneous gravidity. A chorionic biopsy examination of this gravidity ascertained the female sex and a pericentric inversion of chromosome 5 in 70% of the cultivated foetal cells.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Using indirect linkage analysis, PGD may help to identify genetic X-linked defects within embryos during screening, thereby circumventing the potential problems with abortion.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Presentar un enfoque metodológico del diagnóstico genético preimplantacional (DGP) como opción para embarazos no afectados en parejas en edad reproductiva con riesgo genético de neuropatía periférica dominante por enfermedad de Charcot-Marie-Tooth tipo 1 ligada al cromosoma X.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Llevamos a cabo el DGP de enfermedad de Charcot-Marie-Tooth tipo 1 ligada al cromosoma X utilizando un análisis de ligamiento indirecto/haplotificación, durante el cual logramos excluir los embriones portadores de un haplotipo de alto riesgo ligado a la mutación causal p.Leu9Phe en el gen <span class="elsevierStyleItalic">GJB1</span>.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Dentro del ciclo de DGP, examinamos 4 blastómeros biopsiados de los embriones en fase de división, y recomendamos la transferencia de 3 embriones. Dos embriones fueron implantados en el útero; sin embargo, el resultado fue un embarazo único con un descendiente varón. Transcurridos 3 años, la pareja regresó con un embarazo espontáneo. La biopsia coriónica de este embarazo reveló el sexo femenino y una inversión pericéntrica del cromosoma 5 en el 70% de las células fetales cultivadas.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Utilizando el análisis de ligamiento indirecto, el DGP puede ayudar a identificar durante el cribado los defectos genéticos ligados al cromosoma X, eludiendo por tanto los problemas potenciales con el aborto.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Borgulová I, Putzová M, Soldatova I, Stejskal D. Diagnóstico genético preimplantacional de la enfermedad de Charcot-Marie-Tooth ligada al cromosoma X mediante análisis de ligamiento indirecto. Med Clin (Barc). 2018;150:215–219.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 795 "Ancho" => 2249 "Tamanyo" => 72674 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Pedigree of family show an inheritance of X-linked mutation c.27G¿T where female proband (<span class="elsevierStyleItalic">year of birth</span>) is marked by arrow.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1710 "Ancho" => 1347 "Tamanyo" => 164886 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Sequencing data presented detection of the c.27G¿T mutation in intercepted family members.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 3080 "Ancho" => 2917 "Tamanyo" => 814531 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Haplotypes of the reproductive-age couple, along with those of the female proband's mother and uncle. (A) Based on a comparison of DNA profiles within the <span class="elsevierStyleItalic">GJB1</span> gene among family members, low-risk and high-risk haplotypes were identified. (B) Possible haplotypes of the embryo derived from both partners, together with informative healthy/pathologic alleles. Unlabelled alleles are not informative. <span class="elsevierStyleItalic">Haplotype consideration: red – maternal high-risk haplotype, green – maternal low-risk haplotype, and blue – paternal low-risk haplotype</span>.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">F-forward, R-reverse</p>" "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"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">STR marker \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Genetic distance [cM]<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Heterozygozity (HET)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Size [bp] \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Fluorescent tagging \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">F-primer \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">R-primer \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS8040 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">164 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FAM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ACCCGACTGGCTATCATTTTAAG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GAGATCTGTAGGCTGATTTGACAC \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS1216 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">239 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FAM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CAACAGTGCTAAGGATCAATGCTA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AGAAGACTTGCCCATCTGTTTAGA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS8111 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">235 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FAM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TGTTATTTGCTTCCCTTGCAT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CCTCCCTAACACCCATGTTG \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS1275 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">204 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NED \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AGGATGGTTGTGAGGATTCG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ACAAGGTCTGGAAGGCTGTG \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS8031 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">271 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">VIC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CGTGGCCTCTACACTGGTTT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TGCCTAGAATGATGCCTGGT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS983 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">186 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TTCACTCCTGCAGCTATCACA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TACCTGCCTCTGGCTTTCTG \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS8107 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">103 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FAM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CGGTGTGCTGTTCAAGTTGT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ACCTTCCCAATGTTTCAGGA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS8052 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">131 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GGGCAATTTATGCACAAGAG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TGGTAGCACATCCAGCTGTT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">21xTG<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">/ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">249 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NED \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GGAGTCCGAGGCTGAATGTA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GGAGTTTGCATTCTGAGACCA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">11xTTTA<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">/ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">133 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ATGCTGGTTGGCACATGAC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GACAGTCCACAGGACATAGGTTACT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS8101 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">291 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FAM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TGCCTGACAGCCTAAGGGTA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GAACCCAGGAGGCAGTGAC \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS8046 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">268 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CAGATCGTGGTTTGTGGTTG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TGCCATTTACCCAGGTTCTT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS8070 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">266 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">VIC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CAGCACGAGAACAGACTAAAACAT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TTGTCCAAAATAGAAATAGCAACC \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS8079 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">141 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">VIC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TTCTTTCAAACCAGGAGCATG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TTCAACCAAGGAGGTGAAAGA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS8060 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">177 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">VIC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AACGAACACAGCCATGTCCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TGTGGGCATATTTCTCTGACA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS8092 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">164 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NED \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ATTCCCAGTCCTGGAGTCCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CAGGGCTAGAAAGCCACAAG \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS8037 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">162 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FAM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CTCCCAGCAAGCCTTCATAG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GCAAGACATCCATTCCCAAC \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DXS1221 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">222 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NED \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GCATAATCTCCACTGATCTTCCTT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CTTAGAAGTGGCCCAGATGACTT \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1710424.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Genetic distance and heterozygozity (HET) was elicited from Marshfield Comprehensive human genetic map.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Intragenic STR markers are labelled yellowish.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">The list of STR markers and the sequence of the fluorescent primers applied to the PGH panel of the GJB1 gene.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Charcot-Marie-Tooth neuropathy X type 1" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.T. 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Supported by Ministry of Health of the Czech Republic AZV 1630206A and DRO 00064203.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015000000006/v1_201803290432/S2387020618300263/v1_201803290432/en/main.assets" "Apartado" => array:4 [ "identificador" => "43310" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015000000006/v1_201803290432/S2387020618300263/v1_201803290432/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618300263?idApp=UINPBA00004N" ]
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Preimplantation genetic diagnosis of X-linked Charcot-Marie-Tooth disease by indirect linkage analysis
Diagnóstico genético preimplantacional de la enfermedad de Charcot-Marie-Tooth ligada al cromosoma X mediante análisis de ligamiento indirecto