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Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease, involving changes in ventricular myocardial tissue and leading to fatal arrhythmias. Mutations in desmosomal genes are thought to be the main cause of ARVC. However, the exact molecular genetic etiolo...

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Autores principales: Qadri, Sami, Anttonen, Olli, Viikilä, Juho, Seppälä, Eija H., Myllykangas, Samuel, Alastalo, Tero-Pekka, Holmström, Miia, Heliö, Tiina, Koskenvuo, Juha W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561604/
https://www.ncbi.nlm.nih.gov/pubmed/28818065
http://dx.doi.org/10.1186/s12881-017-0442-3
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author Qadri, Sami
Anttonen, Olli
Viikilä, Juho
Seppälä, Eija H.
Myllykangas, Samuel
Alastalo, Tero-Pekka
Holmström, Miia
Heliö, Tiina
Koskenvuo, Juha W.
author_facet Qadri, Sami
Anttonen, Olli
Viikilä, Juho
Seppälä, Eija H.
Myllykangas, Samuel
Alastalo, Tero-Pekka
Holmström, Miia
Heliö, Tiina
Koskenvuo, Juha W.
author_sort Qadri, Sami
collection PubMed
description BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease, involving changes in ventricular myocardial tissue and leading to fatal arrhythmias. Mutations in desmosomal genes are thought to be the main cause of ARVC. However, the exact molecular genetic etiology of the disease still remains largely inconclusive, and this along with large variabilities in clinical manifestations complicate clinical diagnostics. CASE PRESENTATION: We report two families (n = 20) in which a desmoglein-2 (DSG2) missense variant c.1003A > G, p.(Thr335Ala) was discovered in the index patients using next-generation sequencing panels. The presence of this variant in probands’ siblings and children was studied by Sanger sequencing. Five homozygotes and nine heterozygotes were found with the mutation. Participants were evaluated clinically where possible, and available medical records were obtained. All patients homozygous for the variant fulfilled the current diagnostic criteria for ARVC, whereas none of the heterozygous subjects had symptoms suggestive of ARVC or other cardiomyopathies. CONCLUSIONS: The homozygous DSG2 variant c.1003A > G co-segregated with ARVC, indicating autosomal recessive inheritance and complete penetrance. More research is needed to establish a detailed understanding of the relevance of rare variants in ARVC associated genes, which is essential for informative genetic counseling and rational family member testing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-017-0442-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-55616042017-08-18 Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2 Qadri, Sami Anttonen, Olli Viikilä, Juho Seppälä, Eija H. Myllykangas, Samuel Alastalo, Tero-Pekka Holmström, Miia Heliö, Tiina Koskenvuo, Juha W. BMC Med Genet Case Report BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease, involving changes in ventricular myocardial tissue and leading to fatal arrhythmias. Mutations in desmosomal genes are thought to be the main cause of ARVC. However, the exact molecular genetic etiology of the disease still remains largely inconclusive, and this along with large variabilities in clinical manifestations complicate clinical diagnostics. CASE PRESENTATION: We report two families (n = 20) in which a desmoglein-2 (DSG2) missense variant c.1003A > G, p.(Thr335Ala) was discovered in the index patients using next-generation sequencing panels. The presence of this variant in probands’ siblings and children was studied by Sanger sequencing. Five homozygotes and nine heterozygotes were found with the mutation. Participants were evaluated clinically where possible, and available medical records were obtained. All patients homozygous for the variant fulfilled the current diagnostic criteria for ARVC, whereas none of the heterozygous subjects had symptoms suggestive of ARVC or other cardiomyopathies. CONCLUSIONS: The homozygous DSG2 variant c.1003A > G co-segregated with ARVC, indicating autosomal recessive inheritance and complete penetrance. More research is needed to establish a detailed understanding of the relevance of rare variants in ARVC associated genes, which is essential for informative genetic counseling and rational family member testing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-017-0442-3) contains supplementary material, which is available to authorized users. BioMed Central 2017-08-17 /pmc/articles/PMC5561604/ /pubmed/28818065 http://dx.doi.org/10.1186/s12881-017-0442-3 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.
spellingShingle Case Report
Qadri, Sami
Anttonen, Olli
Viikilä, Juho
Seppälä, Eija H.
Myllykangas, Samuel
Alastalo, Tero-Pekka
Holmström, Miia
Heliö, Tiina
Koskenvuo, Juha W.
Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2
title Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2
title_full Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2
title_fullStr Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2
title_full_unstemmed Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2
title_short Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2
title_sort case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous thr335ala variant in dsg2
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561604/
https://www.ncbi.nlm.nih.gov/pubmed/28818065
http://dx.doi.org/10.1186/s12881-017-0442-3
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