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Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients
BACKGROUND: Genetic testing in hypertrophic cardiomyopathy (HCM) is a published guideline-based recommendation. The diagnostic yield of genetic testing and corresponding HCM-associated genes have been largely documented by single center studies and carefully selected patient cohorts. Our goal was to...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934228/ https://www.ncbi.nlm.nih.gov/pubmed/33673806 http://dx.doi.org/10.1186/s12872-021-01927-5 |
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author | Hathaway, Julie Heliö, Krista Saarinen, Inka Tallila, Jonna Seppälä, Eija H. Tuupanen, Sari Turpeinen, Hannu Kangas-Kontio, Tiia Schleit, Jennifer Tommiska, Johanna Kytölä, Ville Valori, Miko Muona, Mikko Sistonen, Johanna Gentile, Massimiliano Salmenperä, Pertteli Myllykangas, Samuel Paananen, Jussi Alastalo, Tero-Pekka Heliö, Tiina Koskenvuo, Juha |
author_facet | Hathaway, Julie Heliö, Krista Saarinen, Inka Tallila, Jonna Seppälä, Eija H. Tuupanen, Sari Turpeinen, Hannu Kangas-Kontio, Tiia Schleit, Jennifer Tommiska, Johanna Kytölä, Ville Valori, Miko Muona, Mikko Sistonen, Johanna Gentile, Massimiliano Salmenperä, Pertteli Myllykangas, Samuel Paananen, Jussi Alastalo, Tero-Pekka Heliö, Tiina Koskenvuo, Juha |
author_sort | Hathaway, Julie |
collection | PubMed |
description | BACKGROUND: Genetic testing in hypertrophic cardiomyopathy (HCM) is a published guideline-based recommendation. The diagnostic yield of genetic testing and corresponding HCM-associated genes have been largely documented by single center studies and carefully selected patient cohorts. Our goal was to evaluate the diagnostic yield of genetic testing in a heterogeneous cohort of patients with a clinical suspicion of HCM, referred for genetic testing from multiple centers around the world. METHODS: A retrospective review of patients with a suspected clinical diagnosis of HCM referred for genetic testing at Blueprint Genetics was undertaken. The analysis included syndromic, myopathic and metabolic etiologies. Genetic test results and variant classifications were extracted from the database. Variants classified as pathogenic (P) or likely pathogenic (LP) were considered diagnostic. RESULTS: A total of 1376 samples were analyzed. Three hundred and sixty-nine tests were diagnostic (26.8%); 373 P or LP variants were identified. Only one copy number variant was identified. The majority of diagnostic variants involved genes encoding the sarcomere (85.0%) followed by 4.3% of diagnostic variants identified in the RASopathy genes. Two percent of diagnostic variants were in genes associated with a cardiomyopathy other than HCM or an inherited arrhythmia. Clinical variables that increased the likelihood of identifying a diagnostic variant included: an earlier age at diagnosis (p < 0.0001), a higher maximum wall thickness (MWT) (p < 0.0001), a positive family history (p < 0.0001), the absence of hypertension (p = 0.0002), and the presence of an implantable cardioverter-defibrillator (ICD) (p = 0.0004). CONCLUSION: The diagnostic yield of genetic testing in this heterogeneous cohort of patients with a clinical suspicion of HCM is lower than what has been reported in well-characterized patient cohorts. We report the highest yield of diagnostic variants in the RASopathy genes identified in a laboratory cohort of HCM patients to date. The spectrum of genes implicated in this unselected cohort highlights the importance of pre-and post-test counseling when offering genetic testing to the broad HCM population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-021-01927-5. |
format | Online Article Text |
id | pubmed-7934228 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-79342282021-03-05 Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients Hathaway, Julie Heliö, Krista Saarinen, Inka Tallila, Jonna Seppälä, Eija H. Tuupanen, Sari Turpeinen, Hannu Kangas-Kontio, Tiia Schleit, Jennifer Tommiska, Johanna Kytölä, Ville Valori, Miko Muona, Mikko Sistonen, Johanna Gentile, Massimiliano Salmenperä, Pertteli Myllykangas, Samuel Paananen, Jussi Alastalo, Tero-Pekka Heliö, Tiina Koskenvuo, Juha BMC Cardiovasc Disord Research Article BACKGROUND: Genetic testing in hypertrophic cardiomyopathy (HCM) is a published guideline-based recommendation. The diagnostic yield of genetic testing and corresponding HCM-associated genes have been largely documented by single center studies and carefully selected patient cohorts. Our goal was to evaluate the diagnostic yield of genetic testing in a heterogeneous cohort of patients with a clinical suspicion of HCM, referred for genetic testing from multiple centers around the world. METHODS: A retrospective review of patients with a suspected clinical diagnosis of HCM referred for genetic testing at Blueprint Genetics was undertaken. The analysis included syndromic, myopathic and metabolic etiologies. Genetic test results and variant classifications were extracted from the database. Variants classified as pathogenic (P) or likely pathogenic (LP) were considered diagnostic. RESULTS: A total of 1376 samples were analyzed. Three hundred and sixty-nine tests were diagnostic (26.8%); 373 P or LP variants were identified. Only one copy number variant was identified. The majority of diagnostic variants involved genes encoding the sarcomere (85.0%) followed by 4.3% of diagnostic variants identified in the RASopathy genes. Two percent of diagnostic variants were in genes associated with a cardiomyopathy other than HCM or an inherited arrhythmia. Clinical variables that increased the likelihood of identifying a diagnostic variant included: an earlier age at diagnosis (p < 0.0001), a higher maximum wall thickness (MWT) (p < 0.0001), a positive family history (p < 0.0001), the absence of hypertension (p = 0.0002), and the presence of an implantable cardioverter-defibrillator (ICD) (p = 0.0004). CONCLUSION: The diagnostic yield of genetic testing in this heterogeneous cohort of patients with a clinical suspicion of HCM is lower than what has been reported in well-characterized patient cohorts. We report the highest yield of diagnostic variants in the RASopathy genes identified in a laboratory cohort of HCM patients to date. The spectrum of genes implicated in this unselected cohort highlights the importance of pre-and post-test counseling when offering genetic testing to the broad HCM population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-021-01927-5. BioMed Central 2021-03-05 /pmc/articles/PMC7934228/ /pubmed/33673806 http://dx.doi.org/10.1186/s12872-021-01927-5 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Hathaway, Julie Heliö, Krista Saarinen, Inka Tallila, Jonna Seppälä, Eija H. Tuupanen, Sari Turpeinen, Hannu Kangas-Kontio, Tiia Schleit, Jennifer Tommiska, Johanna Kytölä, Ville Valori, Miko Muona, Mikko Sistonen, Johanna Gentile, Massimiliano Salmenperä, Pertteli Myllykangas, Samuel Paananen, Jussi Alastalo, Tero-Pekka Heliö, Tiina Koskenvuo, Juha Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients |
title | Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients |
title_full | Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients |
title_fullStr | Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients |
title_full_unstemmed | Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients |
title_short | Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients |
title_sort | diagnostic yield of genetic testing in a heterogeneous cohort of 1376 hcm patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934228/ https://www.ncbi.nlm.nih.gov/pubmed/33673806 http://dx.doi.org/10.1186/s12872-021-01927-5 |
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