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Saraiva" "autores" => array:1 [ 0 => array:4 [ "nombre" => "Jorge M." "apellidos" => "Saraiva" "email" => array:1 [ 0 => "j.saraiva@chuc.min-saude.pt" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Medical Genetics Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "University Clinic of Pediatrics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Os testes genéticos na avaliação de doentes e familiares – o exemplo da miocardiopatia hipertrófica" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The article “Clinical and genetic diagnosis of familial hypertrophic cardiomyopathy: results in pediatric cardiology” by Cardoso et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> published in this issue of the <span class="elsevierStyleItalic">Journal</span> is a good illustration of the current and future implications of genetic tests.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Genetic testing, mainly regulated in Portugal by Act 12/2005 and Decree-Law 131/2014, is becoming increasingly common as a complementary or first-line diagnostic method and continues to develop rapidly. This can be seen in the case of hypertrophic cardiomyopathy (HCM), in which sequencing of the entire coding region and intron/exon boundaries of seven genes is now routinely performed to screen for pathogenic or potentially pathogenic mutations that are found in 60-65% of cases.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> Increasing the number of genes studied shows only marginal gains – 60-70% positivity for 29 genes.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Whole exome sequencing will shortly be generally available, and will then be replaced by whole genome sequencing. The growing quantity of information will require ever-increasing rigor in interpreting the results, and those performing genetic testing will have to include in their report not only the method used and the results, but also their interpretation of the findings and appropriate recommendations for each clinical context. At present, the 2015 guidelines of the American College of Medical Genetics and Genomics, which specify how to classify sequence variants as pathogenic, likely pathogenic, of uncertain significance, likely benign or benign, should be used by preference.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The prevalence of HCM in the general population is often reported as 1:500<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> and a genetic cause is confirmed in more than 50% of cases, which leads us to question why only 10 families were included, three with pediatric and seven with adult probands, with positive genetic tests over a 10-year period. Advances in genetic testing and more widespread use will no doubt lead to rapid growth in the percentage with a known genetic cause. The fact that the sample included cases of greater severity and/or visibility may explain why initial cardiological assessment was performed at a median age at the lower limit of that recommended (10 years) and why pathogenic sequence variants were identified in 14 (or 15) of the 20 cases. Grouping the results for the three pediatric probands with those of the 17 first-degree relatives of HCM patients makes it difficult to determine the age at which the first cardiological assessment was performed in the latter group (which certainly does not include the infant who was assessed at one month of age). The detection of a pathogenic sequence variant in 11 (or 12) of the 17 relatives (65-71%) and a positive phenotype in four of the 11 (or 12) at initial assessment also points to possible sampling bias.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The genes tested were the six reported to be responsible for most cases of HCM (<span class="elsevierStyleItalic">MYH7</span>: 40%, <span class="elsevierStyleItalic">MYPBC3</span>: 40%, <span class="elsevierStyleItalic">TNNT2</span>: 5%, <span class="elsevierStyleItalic">TNNI3</span>: 5%, <span class="elsevierStyleItalic">TPM1</span>: 2%, <span class="elsevierStyleItalic">MYL3</span>: 1%)<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> and two others (<span class="elsevierStyleItalic">MYL2</span> and <span class="elsevierStyleItalic">ACTC1</span>). All the mutations identified were among the first group. The analysis of the distribution of sequence variants is limited by the sample size and by the inclusion of 18 mutations in 14 children, including variants that are of uncertain significance or probably benign.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The lack of a confirmed genetic diagnosis and the fact that HCM is most often of autosomal dominant inheritance with incomplete penetrance and variable expression means that regular assessment of relatives of each index case is essential, given the benefits to the individuals concerned, including prevention of sudden cardiac death.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Identifying a genetic cause of the disease in a proband enables all relatives of an appropriate age (10-12 years) to be assessed in order to determine the indication for surveillance (electrocardiography, 24-hour Holter monitoring, conventional exercise testing, standard echocardiography, transthoracic echocardiography and exercise echocardiography, and possibly also magnetic resonance imaging<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a>), and to confirm or exclude the presence of a pathogenic sequence variant. Predictive genetic tests require free and informed written consent under the terms of Directorate-General of Health regulations<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> and must be performed in medical genetics consultations. The results enable relatives at no risk to be discharged from follow-up, while highlighting the importance of surveillance and treatment in those at risk.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Genetic testing also assists with counseling for individuals and couples and with reproductive health issues, but it has its limitations, since at present it is not possible to determine in what form or when the disease may appear or how it will progress, and so other diagnostic methods are still required.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The article by Cardoso et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> is not only of particular interest to those involved in treating patients with HCM and their relatives, but it also invites reflection on the most appropriate approach to implementing diagnostic genetic testing in other patient groups in cardiology or other medical specialties.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Saraiva JM. Os testes genéticos na avaliação de doentes e familiares – o exemplo da miocardiopatia hipertrófica. Rev Port Cardiol. 2017;36:167–168.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnóstico clínico e genético de miocardiopatia hipertrófica familiar: resultados em cardiologia pediátrica" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "B. Cardoso" 1 => "I. Gomes" 2 => "P. 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Year/Month | Html | Total | |
---|---|---|---|
2024 November | 5 | 9 | 14 |
2024 October | 29 | 18 | 47 |
2024 September | 32 | 22 | 54 |
2024 August | 29 | 29 | 58 |
2024 July | 25 | 24 | 49 |
2024 June | 27 | 19 | 46 |
2024 May | 24 | 20 | 44 |
2024 April | 31 | 26 | 57 |
2024 March | 32 | 29 | 61 |
2024 February | 25 | 46 | 71 |
2024 January | 17 | 33 | 50 |
2023 December | 23 | 25 | 48 |
2023 November | 23 | 18 | 41 |
2023 October | 15 | 11 | 26 |
2023 September | 23 | 21 | 44 |
2023 August | 19 | 15 | 34 |
2023 July | 19 | 11 | 30 |
2023 June | 26 | 12 | 38 |
2023 May | 26 | 21 | 47 |
2023 April | 18 | 6 | 24 |
2023 March | 29 | 16 | 45 |
2023 February | 21 | 20 | 41 |
2023 January | 22 | 7 | 29 |
2022 December | 32 | 22 | 54 |
2022 November | 29 | 22 | 51 |
2022 October | 28 | 18 | 46 |
2022 September | 16 | 25 | 41 |
2022 August | 19 | 30 | 49 |
2022 July | 20 | 34 | 54 |
2022 June | 15 | 13 | 28 |
2022 May | 20 | 29 | 49 |
2022 April | 14 | 20 | 34 |
2022 March | 22 | 26 | 48 |
2022 February | 26 | 36 | 62 |
2022 January | 19 | 22 | 41 |
2021 December | 16 | 32 | 48 |
2021 November | 29 | 28 | 57 |
2021 October | 29 | 50 | 79 |
2021 September | 21 | 24 | 45 |
2021 August | 23 | 28 | 51 |
2021 July | 20 | 15 | 35 |
2021 June | 15 | 19 | 34 |
2021 May | 34 | 40 | 74 |
2021 April | 50 | 42 | 92 |
2021 March | 42 | 25 | 67 |
2021 February | 42 | 17 | 59 |
2021 January | 41 | 11 | 52 |
2020 December | 19 | 14 | 33 |
2020 November | 25 | 14 | 39 |
2020 October | 19 | 14 | 33 |
2020 September | 38 | 13 | 51 |
2020 August | 20 | 9 | 29 |
2020 July | 37 | 13 | 50 |
2020 June | 24 | 10 | 34 |
2020 May | 21 | 4 | 25 |
2020 April | 25 | 6 | 31 |
2020 March | 30 | 5 | 35 |
2020 February | 34 | 25 | 59 |
2020 January | 19 | 5 | 24 |
2019 December | 23 | 1 | 24 |
2019 November | 23 | 8 | 31 |
2019 October | 28 | 3 | 31 |
2019 September | 17 | 10 | 27 |
2019 August | 26 | 6 | 32 |
2019 July | 44 | 10 | 54 |
2019 June | 25 | 12 | 37 |
2019 May | 32 | 6 | 38 |
2019 April | 21 | 12 | 33 |
2019 March | 29 | 16 | 45 |
2019 February | 34 | 8 | 42 |
2019 January | 64 | 5 | 69 |
2018 December | 91 | 9 | 100 |
2018 November | 83 | 10 | 93 |
2018 October | 158 | 19 | 177 |
2018 September | 57 | 14 | 71 |
2018 August | 39 | 8 | 47 |
2018 July | 16 | 4 | 20 |
2018 June | 38 | 6 | 44 |
2018 May | 41 | 6 | 47 |
2018 April | 66 | 6 | 72 |
2018 March | 64 | 9 | 73 |
2018 February | 40 | 7 | 47 |
2018 January | 58 | 14 | 72 |
2017 December | 77 | 10 | 87 |
2017 November | 48 | 6 | 54 |
2017 October | 38 | 7 | 45 |
2017 September | 36 | 11 | 47 |
2017 August | 45 | 14 | 59 |
2017 July | 32 | 13 | 45 |
2017 June | 55 | 11 | 66 |
2017 May | 61 | 26 | 87 |
2017 April | 51 | 17 | 68 |
2017 March | 47 | 17 | 64 |