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

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http://hdl.handle.net/10138/224209

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Qadri , S , Anttonen , O , Viikila , J , Seppälä , E H , Myllykangas , S , Alastalo , T-P , Holmström , M , Helio , T & Koskenvuo , J W 2017 , ' Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2 ' , BMC Medical Genetics , vol. 18 , 86 . https://doi.org/10.1186/s12881-017-0442-3

Title: Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2
Author: Qadri, Sami; Anttonen, Olli; Viikila, Juho; Seppälä, Eija H.; Myllykangas, Samuel; Alastalo, Tero-Pekka; Holmström, Miia; Helio, Tiina; Koskenvuo, Juha W.
Contributor: University of Helsinki, HUS Heart and Lung Center
University of Helsinki, Medicum
University of Helsinki, Clinicum
University of Helsinki, HUS Medical Imaging Center
University of Helsinki, Department of Medicine
University of Helsinki, Department of Diagnostics and Therapeutics
Date: 2017-08-17
Language: eng
Number of pages: 9
Belongs to series: BMC Medical Genetics
ISSN: 1471-2350
URI: http://hdl.handle.net/10138/224209
Abstract: 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.
Subject: Arrhythmogenic right ventricular cardiomyopathy
Cardiomyopathies
Desmosomes
DSG2
Mutation
Case series
DESMOSOMAL MUTATION CARRIERS
PROTEIN GENE-MUTATIONS
TASK-FORCE CRITERIA
DILATED CARDIOMYOPATHY
PALMOPLANTAR KERATODERMA
SUDDEN-DEATH
WOOLLY HAIR
DYSPLASIA/CARDIOMYOPATHY
DYSPLASIA
PREVALENCE
3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
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