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"/23870206/0000015300000007/v2_201910291451/S238702061930405X/v2_201910291451/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>" "titulo" => "Recommendations for the preparation of diagnostic genetic reports in the clinical setting" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "293" "paginaFinal" => "297" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Josep Oriola, Pilar Carrasco, Orland Díez, Begoña Ezquieta" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Josep" "apellidos" => "Oriola" "email" => array:1 [ 0 => "joriola@clinic.cat" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Pilar" "apellidos" => "Carrasco" ] 2 => array:2 [ "nombre" => "Orland" "apellidos" => "Díez" ] 3 => array:2 [ "nombre" => "Begoña" "apellidos" => "Ezquieta" ] 4 => array:1 [ "colaborador" => "on behalf of the SEQC Genetics Commission" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Bioquímica y Genética Molecular, CDB, Hospital Clínic, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Recomendaciones para la elaboración de informes genéticos dediagnóstico en el ámbito asistencial" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Advances made in recent decades in the field of clinical genetics, with the identification of numerous genes and especially the incorporation of high-efficiency and low-cost genetic analysis technologies have significantly increased the number of requests for genetic studies in many fields of clinical diagnosis.</p><p id="par0010" class="elsevierStylePara elsevierViewall">These studies require special consideration since they are performed only once in a lifetime, the results are often diagnostic and can be useful for possible follow-up or specific treatment, or to predict the risk of developing a disease in a healthy population. Therefore, the results of a genetic study are of considerable significance as they have an impact on the decisions that a person can make for life, which also affect family members. The use of next-generation sequencing or other high-performance technologies has greatly increased the ability to detect genetic variants and, thus, the complexity of their clinical interpretation and their reporting through a laboratory or clinical report.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Thus, for genetic reports to have an optimal structure and content, it is recommended that their preparation follows internationally agreed guidelines,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> which may be adapted as knowledge or methodologies of genetic analysis advance.</p><p id="par0020" class="elsevierStylePara elsevierViewall">This document intends to give recommendations to support the preparation of genetic reports related to hereditary monogenic diseases (dominant, recessive and X ligand) in the field of care. The following sections should be included in the reports: identifying data of the person to be studied, the indications by which the study is carried out, the methodology used, and the results obtained, as well as the interpretation and limitations of the analysis. Expansion, <span class="elsevierStyleItalic">imprinting</span> or mitochondrial hereditary diseases are not included in this document, nor genetic reports resulting from the analysis of tumour tissue.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Informed consent</span><p id="par0025" class="elsevierStylePara elsevierViewall">The patient should receive information about the characteristics of the genetic study that will be performed.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> For this, the doctor who prescribes the study must request the informed consent document from the patient in order to ensure that he understands the purpose and implications of the proposed analysis as specified by the Biomedical Research Law 14/2007 of July 3 (LIB), as well as his right to receive pre- and post-test genetic counseling.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The study may include only certain genes, all of them potentially involved in the patient’s disease, or study a panel of tens, hundreds of genes or directly the exome or genome, which contains both disease-related as well as unrelated genes.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In this second case, the informed consent document must specify whether the patient wants to know about the genetic variants that may have been identified in genes associated with hereditary diseases different from the one that caused the consultation.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The results that can be obtained, such as the identification of clearly or probably pathogenic variants, variants of uncertain significance (the existing knowledge at the time of the analysis does not allow to know their clinical significance) or clearly or probably benign variants that will not be included in the report should be explained to the patient. The possibility of not detecting any genetic variant associated with the patient's disease should also be considered. When genetic counselling is carried out in the context of a prenatal diagnosis, the technical limitations must be clearly indicated according to the type of sample and the delivery time of the result, considering the legal deadlines for termination of pregnancy as described in Organic Law 2/2010 of 3rd March.</p><p id="par0040" class="elsevierStylePara elsevierViewall">All guarantees in relation to genetic analysis and biological samples within the scope of personal data protection, whether in the diagnostic or research field, are covered by the LIB (Spanish acronym for Biomedical Research Law).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Structure and content of genetic reports</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Identification data of the person to study</span><p id="par0045" class="elsevierStylePara elsevierViewall">In every report the name and the two surnames must be included in addition to one or two codes (e.g., request number, medical history number), as well as the date of birth, gender and the source of the DNA. The most common is venous blood, but it can be a mouthwash, chorionic villus, amniotic fluid, biopsy, etc.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In a prenatal analysis of a foetal sample, the report is identified with the name of the pregnant woman or a code, if its confidentiality must be legally preserved, clearly specifying the type of sample analysed (chorionic villus, amniotic fluid or others). Likewise, it should be indicated if maternal contamination has been ruled out by contrasting the foetal DNA with the mother’s DNA.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The report must include the name of the requesting physician, the department and the center or laboratory that prepares it. In this way, in the event of any developments that may arise in the future, the interested party may contact the physician or the laboratory issuing the report again.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The sample receipt and report writing dates indicate when the analysis was performed and allow greater traceability control, considering the existing methodologies and disease knowledge at the time the report was issued.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Indication of the genetic study</span><p id="par0065" class="elsevierStylePara elsevierViewall">The requesting physician must clearly specify the purpose of the study, indicating whether it is a confirmation study as a result of a clinical diagnosis or if the study is requested based on results obtained from diagnostic tests, whether biochemical or anatomical pathology, functional, radiology or other studies. Prenatal studies would also be included at this point if the diagnostic suspicion has occurred <span class="elsevierStyleItalic">in utero</span>.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The “index case” and the “family case” can be distinguished. The index case is the first individual studied in a family. Generally speaking, the individual involved has had no previous genetic study performed associated with the current pathology, or with a previous non-informative genetic study that now needs to be expanded. The index case may also be an asymptomatic person with a family history that suggests an inherited disease, but without the possibility of analysing a biological sample of any affected relative. The family case is a person, affected (symptomatic) or not (asymptomatic), who is part of a family in which one or more genetic variants, causing or compatible with the disease, have been detected in one or more family members.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Methodology used</span><p id="par0075" class="elsevierStylePara elsevierViewall">This section should describe the genes analysed and the methodology used, either conventional sequencing (Sanger), next-generation sequencing or any other method. A reference must be included for each gene analysed (NM_, NG_, LRG_, etc.). This reference is very important, since the genetic variants found can be described differently and even located in different exons according to the transcript used. The regions (generally exons) of each gene studied should be described and whether other regions (promoter region, intron-flanking exon regions, UTR regions, etc.) have been included.</p><p id="par0080" class="elsevierStylePara elsevierViewall">If next-generation sequencing is used, type of panel used (commercial or developed in the laboratory itself), methodology and platform used, the bioinformatic analysis procedure followed should be detailed, in addition to the coverage (genomic regions really sequenced) and the minimum depth (number of readings) obtained in the study of the genes described in the report. For germline alterations, a minimum coverage of 25–30 readings is usually accepted for each region, although a minimum of 38 readings are necessary if what is sought is a detection of changes that can only occur in 25% of the readings, with an efficiency of 99.9%.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">If the study includes the analysis of the number of copies using MLPA or any other methodology, whether commercial or not, it must also be recorded in the report. The final detection capacity of the study will depend on the genetic analyses performed (DNA sequencing, CNV analysis, RNA studies, etc.).</p><p id="par0090" class="elsevierStylePara elsevierViewall">In family cases, since the genetic variant or variants to be analysed are known, the region of the gene studied (specifying the gene reference) as well as the methodology used (restriction enzyme, Sanger sequencing, MLPA, etc.) must be described. When a relative of an individual that has a certain genetic variant is studied, it is advisable to study in parallel a sample of the individual in which the variant was identified (as a positive control). If the genetic variant is not detected in the relative's sample and a control sample could not be analysed, this limitation should be indicated in the report.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Results</span><p id="par0095" class="elsevierStylePara elsevierViewall">This section should describe the genetic variants found to be causative or compatible with the disease. Common variants present in the general population or variants of a certain gene that, although uncommon, have been clearly described as not associated with the disease should not be reported<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> (benign or probably benign).</p><p id="par0100" class="elsevierStylePara elsevierViewall">The description of the variants must follow the rules of the HGVS,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> which are updated periodically. What is observed in the genetic analysis should be specified, that is, changes in the sequence of the nucleotides, whether substitutions, small deletions or insertions, insertions/deletions (indel), large deletions or duplications, etc. Whenever possible, the change that can be predicted in the protein should be added (amino acid change, stop codon occurrence, reading frame variant, <span class="elsevierStyleItalic">splicing</span> alterations, etc.). Intronic variants should be described as such and specify the distance to the nearest exon. There are web tools, such as Mutalyzer (<a href="https://mutalyzer.nl/">https://mutalyzer.nl/</a>),<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> which are useful for obtaining the correct nomenclature.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Regardless of the type of inheritance model of the disease studied, it should always be specified if the variants detected are homozygous, heterozygous or hemizygous.</p><p id="par0110" class="elsevierStylePara elsevierViewall">If the genetic variant detected has been previously described as causing the disease, it is advisable to add the corresponding literature references. If this is not supported in the literature or in the databases consulted, it must be indicated in the report and the section "Interpretation" (see below). An explanation of the reasons that lead to consider the variant detected as causing the disease should be included.</p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Interpretation</span><p id="par0115" class="elsevierStylePara elsevierViewall">We must consider that a genetic report will be read by the patient and by different professionals who may have different levels of knowledge on genetics, so, in addition to correctly describing the results, their interpretation must be written clearly, concisely and accurately.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The interpretation of the result of the analysis will depend on the type of disease, the inheritance pattern and the result obtained.<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">a)</span><p id="par0125" class="elsevierStylePara elsevierViewall">No genetic variant associated with the disease is detected in an index case</p></li></ul></p><p id="par0130" class="elsevierStylePara elsevierViewall">In this case, it must be informed that the analysis has not confirmed the genetic diagnosis of said disease in the person studied. The limitations of the study should specify if the absence of findings may be due to the fact that the entire gene has not been studied (including promoter region, UTR, etc.), or other known genes that may also be responsible for the disease, or that the technique used does not detect 100% of the variants described as causing the disease. With this result, no genetic study can be carried out on other family members.<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">b)</span><p id="par0135" class="elsevierStylePara elsevierViewall">A variant already described as associated with the disease is detected in an autosomal dominant disease</p></li></ul></p><p id="par0140" class="elsevierStylePara elsevierViewall">If this association has already been described, the supporting evidence must be included in the report. The interpretation must specify that the genetic diagnosis of the disease is confirmed and that the risk of transmitting the variant is 50%, so a genetic cascade testing should be recommended in the family.<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">c)</span><p id="par0145" class="elsevierStylePara elsevierViewall">Two heterozygous variants or one homozygous variant, already described as associated with the disease are detected in an autosomal recessive disease</p></li></ul></p><p id="par0150" class="elsevierStylePara elsevierViewall">Finding a variant in each allele <span class="elsevierStyleItalic">(trans)</span> is very likely, this is known as a compound heterozygous variant. However, there is also the possibility that both variants are in the same allele <span class="elsevierStyleItalic">(cis)</span>. In this case it would be only an unaffected carrier, although there are recessive diseases in which the disease can occur mildly with a single altered allele. For a correct interpretation it must be verified that the variants are <span class="elsevierStyleItalic">trans</span> by conducting a segregation analysis (e.g., by studying the parents). Although it can be assumed that both parents are carriers, this study can reveal whether any of the variants is <span class="elsevierStyleItalic">de novo</span> (appeared in a germ cell, ovum or spermatozoon, from one of the parents, or in the fertilized egg). In addition, the genetic counsellor should warn parents that this study could reveal a false paternity.</p><p id="par0155" class="elsevierStylePara elsevierViewall">If a “apparently homozygous” genetic variant is detected, two possibilities must be considered: that it is really the same alteration in both alleles or that the variant is heterozygous and that the allele not bearing the genetic alteration is deleted, or that, for any other reason, only the allele that shows the point mutation has been amplified and analysed. If some other heterozygous variant is observed in the same amplicon sequencing (e.g., a single nucleotide or SNP variant), this indicates that both alleles have actually been analysed and that the detected variant is homozygous. If this is not the case, large deletion analysis (e.g., through MLPA) should be performed or this variant should be analysed in both parents. Another possibility, although more uncommon, is uniparental disomy, in which the two copies of a chromosome come from the same parent.</p><p id="par0160" class="elsevierStylePara elsevierViewall">A risk of recurrence of 25% can only be predicted after knowing all this information. However, it should be considered that there are very common autosomal recessive diseases (e.g., hemochromatosis or cystic fibrosis) in which the frequency of carriers in the general population is high. When the parents are an affected person and a carrier, the risk of recurrence is 50%. It should be added that if an affected person shows gestational desire, it is recommended that their partner request genetic counselling to assess the need to be studied. In recessive diseases, cascade testing of carriers should also be recommended.<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">d)</span><p id="par0165" class="elsevierStylePara elsevierViewall">A variant already described as associated with the disease is detected in a X chromosome-linked recessive disease</p></li></ul></p><p id="par0170" class="elsevierStylePara elsevierViewall">In this type of disease, genetic variants are hemizygous in men (affected) and women can be heterozygous carriers. When counselling women carriers, they should be informed that they are unlikely to have the disease, although in some cases mild symptoms could occur (e.g., nephrogenic diabetes insipidus or Becker muscular dystrophy). It should also be noted that if genetic alterations are common in the population or there is inbreeding in the family, women may present the disease by having both alleles altered (e.g., colour blindness).</p><p id="par0175" class="elsevierStylePara elsevierViewall">The report should recommend the genetic study in the maternal branch (study of carriers) and indicate that male children of female carriers have a 50% chance of inheriting the genetic alteration (and being affected). Likewise, daughters have a 50% chance of being carriers (unaffected or weakly affected). If the report corresponds to the result of a study in an affected male (and carrier of the pathogenic variant), the genetic counselling is different: their sons will not inherit the variant while the daughters will inherit it.</p><p id="par0180" class="elsevierStylePara elsevierViewall">However, for family planning advice, both the paternal genotype and the maternal genetic inheritance must be considered.<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">e)</span><p id="par0185" class="elsevierStylePara elsevierViewall">A variant not described in the literature, or in the databases, is detected for the disease studied</p></li></ul></p><p id="par0190" class="elsevierStylePara elsevierViewall">It is increasingly common (especially since the use of next-generation sequencing) to detect genetic variants not described in index cases. In some of them it is difficult to determine whether the variant is the cause of the disease or is simply a benign variant.</p><p id="par0195" class="elsevierStylePara elsevierViewall">This assessment is extremely important, since it will determine the inclusion of the patient in a certain syndrome, with the corresponding associated risks; also, the recommendations offered to the patient, both on prevention or early detection as well as therapy, including prophylactic surgery will depend on it. In addition, if the variant is classified as causative, other relatives (parents, siblings, children, etc.) will be studied, providing them with the corresponding genetic counselling according to the type of inheritance.</p><p id="par0200" class="elsevierStylePara elsevierViewall">For the correct clinical classification of genetic variants, different evidences should often be used, looking first for information in the literature or in general or specific databases of the studied gene, as well as in population databases, such as ExAC, gnomAD, 1000-genomes, dbSNP and ClinVar (see websites in Richards et al., 2015).<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">The type of variant detected and its possible effect on the protein should also be assessed, whether it is a nucleotide change that does not result in any amino acid change (synonym variant), a variant that predicts an amino acid change, a stop codon, or a change in the reading frame, or that is located in the exon-intron region possibly affecting the transcription process.</p><p id="par0210" class="elsevierStylePara elsevierViewall">Computer programs that predict <span class="elsevierStyleItalic">in silico</span> the effect of the variant on the protein or on the <span class="elsevierStyleItalic">splicing</span> (intron removal during the mRNA maturation process) can be used. Polyphen, SIFT, Mutation Taster or MutPred2 are among the most used to assess the potential alterations in the structure and function of the corresponding protein, and there are several predictors to assess potential <span class="elsevierStyleItalic">splicing</span> alterations, such as Splice Site Finder, BDGP or MaxEntScan, among others (see websites in Richards et al.).<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">in silico</span> tools used can be mentioned in the report, although they only provide theoretical predictions that, in many cases, do not fit the real effect of the variant; so the clinical classification of a variant should not be based solely on <span class="elsevierStyleItalic">in silico</span> predictions. A cDNA study should be performed for variants that may alter <span class="elsevierStyleItalic">splicing</span> if their effect in vitro has not been described in the literature, requesting a new sample if necessary.</p><p id="par0220" class="elsevierStylePara elsevierViewall">The variant should be analysed with all the available information, following the guidelines indicated by the <span class="elsevierStyleItalic">American College of Medical Genetics and Genomics</span>,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> for which there are online applications (<a href="http://www.medschool.umaryland.edu/genetic_variant_interpretation_tool2.html/">http://www.medschool.umaryland.edu/genetic_variant_interpretation_tool2.html/</a>), which predict if the variant is benign, probably benign, of uncertain clinical significance, probably pathogenic or pathogenic. These guidelines can be periodically refined,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> and specific guidelines have been generated for specific genes, such as hereditary cancer (Enigma consortium: <a href="https://enigmaconsortium.org/">https://enigmaconsortium.org/</a>).<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,12</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">There is controversy about the advisability of reporting variants of unknown clinical significance,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> but if they are included in the report it should be done in a section that clearly indicates that its meaning is uncertain, that it cannot be used for clinical decisions at present, and that its interpretation can be clarified in the future with the advent of new knowledge about the gene or disease. However, in some families with numerous affected and unaffected individuals, a co-segregation analysis of the variant with the disease may be helpful. For this, the type of inheritance must be considered and whether the disease is common in the population, since it increases the possibility of analysing non-carrier individuals with the same phenotype (phenocopies).</p><p id="par0230" class="elsevierStylePara elsevierViewall">A periodic review of uncertain significance variants is also recommended in case there is new available evidence that allows reclassifying the variant.<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">f)</span><p id="par0235" class="elsevierStylePara elsevierViewall">The study of relatives should distinguish between a diagnostic (affected person) or predictive (asymptomatic person) analysis.</p></li></ul></p><p id="par0240" class="elsevierStylePara elsevierViewall">If the person is affected and shows the variant, the interpretation must state that hereditary disease is confirmed. If the variant is not detected, the result does not confirm the disease and a phenocopy should be considered. If the person is asymptomatic and shows the variant, it must be stated that he has a certain risk of developing the disease throughout his life (depending on the penetrance and, sometimes, the gender). The possibility of variant transmission to the offspring should also be specified and that a genetic study in first-degree relatives is recommended. If there are no symptoms and the family variant is not detected, the risk of developing the disease due to the family's genetic variant is nil.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Limitations</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Sensitivity</span><p id="par0245" class="elsevierStylePara elsevierViewall">In cases where no variant associated with the disease is detected, the limitations should be specified, if any; for example, if the gene promoter region in which pathogenic genetic variants have been described has not been studied, if the genetic study of large deletions or duplications has not been performed, or if only one of the several genes that have been involved in a disease has been studied, even though some describe a low percentage of cases.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Specificity</span><p id="par0250" class="elsevierStylePara elsevierViewall">The existence of false positives is very unlikely in cases where genetic variants causing the disease studied are detected. In most genetic studies the specificity is practically 100%. False positives should be considered if there are pseudogenes or an apparent “deletion” is observed when using MLPA, which may be due to the presence of a genetic variant that does not allow probe hybridization (this does not occur if the analysis has been performed with software based on next-generation sequencing results). Another possible cause of false positives is to consider a sequencing artifact as a real genetic variant. The possibility of maternal contamination should be indicated in prenatal studies and, if the sample comes from chorionic villus, consider the possibility of a confined placental mosaicism.</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Signature</span><p id="par0255" class="elsevierStylePara elsevierViewall">The report must include the physician's signature (manual or electronic) and the site where the analysis was performed. It is recommended that there be at least two signatures of different doctors and depending on the autonomous community it may be necessary to indicate the current active professional association membership. Indication of the laboratory's quality certifications is recommended and whether it participates in external quality control programs (e.g., EMQN).</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Other recommendations</span><p id="par0260" class="elsevierStylePara elsevierViewall">Attention should be paid to the use of prefabricated templates to prepare the report, avoiding «copy-paste» as much as possible: although they facilitate the writing of the report, they increase the likelihood of making mistakes.</p><p id="par0265" class="elsevierStylePara elsevierViewall">If possible, the report should only occupy one page. If more pages are required, the page number and total must be indicated (e.g.: 1/3 indicates that it is the first page of a total of three).</p><p id="par0270" class="elsevierStylePara elsevierViewall">The reports are confidential and should only contain the information corresponding to the individual analysed. If the person involved is a relative of the index case, mention that the presence of a variant “shown in other family members” is being analysed, omitting, if possible, data belonging to other individuals.</p><p id="par0275" class="elsevierStylePara elsevierViewall">Report models for certain inherited diseases can be found on the EMQN website (<a href="https://www.emqn.org/emqn/Best+Practice">https://www.emqn.org/emqn/Best+Practice</a>) or on gene cards (<a href="https://www.ncbi.nlm.nih.gov/pubmed?term=EJHG%20clinical%20utility%20gene%20card">https://www.ncbi.nlm.nih.gov/pubmed?term=EJHG%20clinical%20utility%20gene%20card</a>)</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflict of interests</span><p id="par0280" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Informed consent" ] 2 => array:3 [ "identificador" => "sec0015" "titulo" => "Structure and content of genetic reports" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Identification data of the person to study" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Indication of the genetic study" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Methodology used" ] ] ] 3 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Interpretation" ] ] ] 4 => array:3 [ "identificador" => "sec0045" "titulo" => "Limitations" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Sensitivity" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Specificity" ] ] ] 5 => array:2 [ "identificador" => "sec0060" "titulo" => "Signature" ] 6 => array:2 [ "identificador" => "sec0065" "titulo" => "Other recommendations" ] 7 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflict of interests" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-03-12" "fechaAceptado" => "2019-06-03" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Oriola J, Carrasco P, Díez O, Ezquieta B. Recomendaciones para la elaboración de informes genéticos de diagnóstico en el ámbito asistencial. Med Clin (Barc). 2019;153:293–297.</p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:3 [ "apendice" => "<p id="par0290" class="elsevierStylePara elsevierViewall">Additional members of the SEQC Genetics Commission: Atocha Romero, Concepción Alonso, Ana Cuesta, Aitor Delmiro, Hada Macher, Jesús Molano, Raquel Rodríguez, Ana M. Sánchez de Abajo, María Santamaria and Cristina Torreira.</p>" "etiqueta" => "Appendix A. 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Special article
Recommendations for the preparation of diagnostic genetic reports in the clinical setting
Recomendaciones para la elaboración de informes genéticos dediagnóstico en el ámbito asistencial
Josep Oriola
, Pilar Carrasco, Orland Díez, Begoña Ezquieta, on behalf of the SEQC Genetics Commission
Autor para correspondencia
Servicio de Bioquímica y Genética Molecular, CDB, Hospital Clínic, Barcelona, Spain