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Pathogenic Variants in Cardiomyopathy Disorder Genes Underlie Pediatric Myocarditis—Further Impact of Heterozygous Immune Disorder Gene Variants?
Myocarditis is an inflammatory disease of the heart. Pediatric myocarditis with the dilated cardiomyopathy (DCM) phenotype may be caused by likely pathogenic or pathogenic genetic variants [(L)P] in cardiomyopathy (CMP) genes. Systematic analysis of immune disorder gene defects has not been performe...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321514/ https://www.ncbi.nlm.nih.gov/pubmed/35877578 http://dx.doi.org/10.3390/jcdd9070216 |
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author | Seidel, Franziska Laser, Kai Thorsten Klingel, Karin Dartsch, Josephine Theisen, Simon Pickardt, Thomas Holtgrewe, Manuel Gärtner, Anna Berger, Felix Beule, Dieter Milting, Hendrik Schubert, Stephan Klaassen, Sabine Kühnisch, Jirko |
author_facet | Seidel, Franziska Laser, Kai Thorsten Klingel, Karin Dartsch, Josephine Theisen, Simon Pickardt, Thomas Holtgrewe, Manuel Gärtner, Anna Berger, Felix Beule, Dieter Milting, Hendrik Schubert, Stephan Klaassen, Sabine Kühnisch, Jirko |
author_sort | Seidel, Franziska |
collection | PubMed |
description | Myocarditis is an inflammatory disease of the heart. Pediatric myocarditis with the dilated cardiomyopathy (DCM) phenotype may be caused by likely pathogenic or pathogenic genetic variants [(L)P] in cardiomyopathy (CMP) genes. Systematic analysis of immune disorder gene defects has not been performed so far. We analyzed 12 patients with biopsy-proven myocarditis and the DCM phenotype together with their parents using whole-exome sequencing (WES). The WES data were filtered for rare pathogenic variants in CMP (n = 89) and immune disorder genes (n = 631). Twelve children with a median age of 2.9 (1.0–6.8) years had a mean left ventricular ejection fraction of 28% (22–32%) and myocarditis was confirmed by endomyocardial biopsy. Patients with primary immunodeficiency were excluded from the study. Four patients underwent implantation of a ventricular assist device and subsequent heart transplantation. Genetic analysis of the 12 families revealed an (L)P variant in the CMP gene in 8/12 index patients explaining DCM. Screening of recessive immune disorder genes identified a heterozygous (L)P variant in 3/12 index patients. This study supports the genetic impact of CMP genes for pediatric myocarditis with the DCM phenotype. Piloting the idea that additional immune-related genetic defects promote myocarditis suggests that the presence of heterozygous variants in these genes needs further investigation. Altered cilium function might play an additional role in inducing inflammation in the context of CMP. |
format | Online Article Text |
id | pubmed-9321514 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93215142022-07-27 Pathogenic Variants in Cardiomyopathy Disorder Genes Underlie Pediatric Myocarditis—Further Impact of Heterozygous Immune Disorder Gene Variants? Seidel, Franziska Laser, Kai Thorsten Klingel, Karin Dartsch, Josephine Theisen, Simon Pickardt, Thomas Holtgrewe, Manuel Gärtner, Anna Berger, Felix Beule, Dieter Milting, Hendrik Schubert, Stephan Klaassen, Sabine Kühnisch, Jirko J Cardiovasc Dev Dis Article Myocarditis is an inflammatory disease of the heart. Pediatric myocarditis with the dilated cardiomyopathy (DCM) phenotype may be caused by likely pathogenic or pathogenic genetic variants [(L)P] in cardiomyopathy (CMP) genes. Systematic analysis of immune disorder gene defects has not been performed so far. We analyzed 12 patients with biopsy-proven myocarditis and the DCM phenotype together with their parents using whole-exome sequencing (WES). The WES data were filtered for rare pathogenic variants in CMP (n = 89) and immune disorder genes (n = 631). Twelve children with a median age of 2.9 (1.0–6.8) years had a mean left ventricular ejection fraction of 28% (22–32%) and myocarditis was confirmed by endomyocardial biopsy. Patients with primary immunodeficiency were excluded from the study. Four patients underwent implantation of a ventricular assist device and subsequent heart transplantation. Genetic analysis of the 12 families revealed an (L)P variant in the CMP gene in 8/12 index patients explaining DCM. Screening of recessive immune disorder genes identified a heterozygous (L)P variant in 3/12 index patients. This study supports the genetic impact of CMP genes for pediatric myocarditis with the DCM phenotype. Piloting the idea that additional immune-related genetic defects promote myocarditis suggests that the presence of heterozygous variants in these genes needs further investigation. Altered cilium function might play an additional role in inducing inflammation in the context of CMP. MDPI 2022-07-05 /pmc/articles/PMC9321514/ /pubmed/35877578 http://dx.doi.org/10.3390/jcdd9070216 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Seidel, Franziska Laser, Kai Thorsten Klingel, Karin Dartsch, Josephine Theisen, Simon Pickardt, Thomas Holtgrewe, Manuel Gärtner, Anna Berger, Felix Beule, Dieter Milting, Hendrik Schubert, Stephan Klaassen, Sabine Kühnisch, Jirko Pathogenic Variants in Cardiomyopathy Disorder Genes Underlie Pediatric Myocarditis—Further Impact of Heterozygous Immune Disorder Gene Variants? |
title | Pathogenic Variants in Cardiomyopathy Disorder Genes Underlie Pediatric Myocarditis—Further Impact of Heterozygous Immune Disorder Gene Variants? |
title_full | Pathogenic Variants in Cardiomyopathy Disorder Genes Underlie Pediatric Myocarditis—Further Impact of Heterozygous Immune Disorder Gene Variants? |
title_fullStr | Pathogenic Variants in Cardiomyopathy Disorder Genes Underlie Pediatric Myocarditis—Further Impact of Heterozygous Immune Disorder Gene Variants? |
title_full_unstemmed | Pathogenic Variants in Cardiomyopathy Disorder Genes Underlie Pediatric Myocarditis—Further Impact of Heterozygous Immune Disorder Gene Variants? |
title_short | Pathogenic Variants in Cardiomyopathy Disorder Genes Underlie Pediatric Myocarditis—Further Impact of Heterozygous Immune Disorder Gene Variants? |
title_sort | pathogenic variants in cardiomyopathy disorder genes underlie pediatric myocarditis—further impact of heterozygous immune disorder gene variants? |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321514/ https://www.ncbi.nlm.nih.gov/pubmed/35877578 http://dx.doi.org/10.3390/jcdd9070216 |
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