Flavie Ader, Neil Derridj, Anne Claire Brehin, Olivia Domanski, Jean Benoit Baudelet, Pauline Gras, Alice Kuster, Nadir Benbrik, Yann Troadec, Isabelle Denjoy, Ronan Bonnefoy, Constance Beyler, Salima El Chehadeh, Elise Schaeffer, Delphine Dupin-Deguine, Adrien Bloch, Caroline Rooryck, Julie Proukhnitzky, Gilles Bosser, Marie Vincenti, Estelle Gandjbakhch, Philippe Charron, Pascale Richard, Damien Bonnet, Diala Khraiche
{"title":"基因检测对一大批小儿心肌病患者的临床影响。","authors":"Flavie Ader, Neil Derridj, Anne Claire Brehin, Olivia Domanski, Jean Benoit Baudelet, Pauline Gras, Alice Kuster, Nadir Benbrik, Yann Troadec, Isabelle Denjoy, Ronan Bonnefoy, Constance Beyler, Salima El Chehadeh, Elise Schaeffer, Delphine Dupin-Deguine, Adrien Bloch, Caroline Rooryck, Julie Proukhnitzky, Gilles Bosser, Marie Vincenti, Estelle Gandjbakhch, Philippe Charron, Pascale Richard, Damien Bonnet, Diala Khraiche","doi":"10.1016/j.ijcard.2024.132729","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>There are limited data that can explain the earlier penetrance and the different expressivity of pediatric cardiomyopathy (pCM) compared to adult-onset cardiomyopathy (aCM). In addition, the relationship between genotype and pCM results is poorly described.</p><p><strong>Objective: </strong>We compared the genotypes between a cohort of aCM and a cohort of pCM to propose hypotheses on the earlier penetrance and expressivity of pCM. Finally, we report how genetic testing was used to guide genetic counseling in pCM.</p><p><strong>Methods: </strong>253 pCM (<18 years old) and 1466 aCM patients were sequenced on a panel of 67 cardiomyopathy genes. Risk factors for death and heart transplantation were analyzed.</p><p><strong>Results: </strong>In pCM, the variant of interest (VOI) yield was 53.7 % including 24.2 % carrying two VOI. De novo variants represented 11 % of VOI in pCM and 50 % in restrictive pCM. An age at diagnosis younger than 1 year (HR = 2.07, p = 0.029), restrictive phenotype (HR = 2.87, p = 0.03) and the presence of two VOI (HR = 2.97, p = 0.001) were independent risk factors for death or heart transplantation. In comparison with aCM, pCM patients harbored more frequently two VOI (p = 0.02), or de novo variants (p = 4.10<sup>-13</sup>). In addition, the distribution of VOI was different in aCM and pCM. Genotyping of pCM improved genetic counseling in families and led to ten prenatal-diagnosis.</p><p><strong>Conclusions: </strong>Genetic testing provides clues for earlier penetrance of pCM. The presence of two VOI in children with CM is a risk factor for severe and early cardiac events.</p>","PeriodicalId":13710,"journal":{"name":"International journal of cardiology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clinical impact of genetic testing in a large cohort of pediatric cardiomyopathies.\",\"authors\":\"Flavie Ader, Neil Derridj, Anne Claire Brehin, Olivia Domanski, Jean Benoit Baudelet, Pauline Gras, Alice Kuster, Nadir Benbrik, Yann Troadec, Isabelle Denjoy, Ronan Bonnefoy, Constance Beyler, Salima El Chehadeh, Elise Schaeffer, Delphine Dupin-Deguine, Adrien Bloch, Caroline Rooryck, Julie Proukhnitzky, Gilles Bosser, Marie Vincenti, Estelle Gandjbakhch, Philippe Charron, Pascale Richard, Damien Bonnet, Diala Khraiche\",\"doi\":\"10.1016/j.ijcard.2024.132729\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>There are limited data that can explain the earlier penetrance and the different expressivity of pediatric cardiomyopathy (pCM) compared to adult-onset cardiomyopathy (aCM). In addition, the relationship between genotype and pCM results is poorly described.</p><p><strong>Objective: </strong>We compared the genotypes between a cohort of aCM and a cohort of pCM to propose hypotheses on the earlier penetrance and expressivity of pCM. Finally, we report how genetic testing was used to guide genetic counseling in pCM.</p><p><strong>Methods: </strong>253 pCM (<18 years old) and 1466 aCM patients were sequenced on a panel of 67 cardiomyopathy genes. Risk factors for death and heart transplantation were analyzed.</p><p><strong>Results: </strong>In pCM, the variant of interest (VOI) yield was 53.7 % including 24.2 % carrying two VOI. De novo variants represented 11 % of VOI in pCM and 50 % in restrictive pCM. An age at diagnosis younger than 1 year (HR = 2.07, p = 0.029), restrictive phenotype (HR = 2.87, p = 0.03) and the presence of two VOI (HR = 2.97, p = 0.001) were independent risk factors for death or heart transplantation. In comparison with aCM, pCM patients harbored more frequently two VOI (p = 0.02), or de novo variants (p = 4.10<sup>-13</sup>). In addition, the distribution of VOI was different in aCM and pCM. Genotyping of pCM improved genetic counseling in families and led to ten prenatal-diagnosis.</p><p><strong>Conclusions: </strong>Genetic testing provides clues for earlier penetrance of pCM. The presence of two VOI in children with CM is a risk factor for severe and early cardiac events.</p>\",\"PeriodicalId\":13710,\"journal\":{\"name\":\"International journal of cardiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-11-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International journal of cardiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ijcard.2024.132729\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International journal of cardiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ijcard.2024.132729","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Clinical impact of genetic testing in a large cohort of pediatric cardiomyopathies.
Background: There are limited data that can explain the earlier penetrance and the different expressivity of pediatric cardiomyopathy (pCM) compared to adult-onset cardiomyopathy (aCM). In addition, the relationship between genotype and pCM results is poorly described.
Objective: We compared the genotypes between a cohort of aCM and a cohort of pCM to propose hypotheses on the earlier penetrance and expressivity of pCM. Finally, we report how genetic testing was used to guide genetic counseling in pCM.
Methods: 253 pCM (<18 years old) and 1466 aCM patients were sequenced on a panel of 67 cardiomyopathy genes. Risk factors for death and heart transplantation were analyzed.
Results: In pCM, the variant of interest (VOI) yield was 53.7 % including 24.2 % carrying two VOI. De novo variants represented 11 % of VOI in pCM and 50 % in restrictive pCM. An age at diagnosis younger than 1 year (HR = 2.07, p = 0.029), restrictive phenotype (HR = 2.87, p = 0.03) and the presence of two VOI (HR = 2.97, p = 0.001) were independent risk factors for death or heart transplantation. In comparison with aCM, pCM patients harbored more frequently two VOI (p = 0.02), or de novo variants (p = 4.10-13). In addition, the distribution of VOI was different in aCM and pCM. Genotyping of pCM improved genetic counseling in families and led to ten prenatal-diagnosis.
Conclusions: Genetic testing provides clues for earlier penetrance of pCM. The presence of two VOI in children with CM is a risk factor for severe and early cardiac events.
期刊介绍：
The International Journal of Cardiology is devoted to cardiology in the broadest sense. Both basic research and clinical papers can be submitted. The journal serves the interest of both practicing clinicians and researchers.
In addition to original papers, we are launching a range of new manuscript types, including Consensus and Position Papers, Systematic Reviews, Meta-analyses, and Short communications. Case reports are no longer acceptable. Controversial techniques, issues on health policy and social medicine are discussed and serve as useful tools for encouraging debate.
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