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

BMC Medical Genetics

Case Report

Eija H. Seppälä¹  Juha W. Koskenvuo²  Tero-Pekka Alastalo³  Samuel Myllykangas⁴  Juho Viikilä⁵  Olli Anttonen⁵  Miia Holmström⁶  Tiina Heliö⁷  Sami Qadri⁷ 

[1] Blueprint Genetics, Helsinki, Finland;Blueprint Genetics, Helsinki, Finland;Department of Clinical Physiology and Nuclear Medicine, HUS Medical Imaging Center, Helsinki University Hospital and University of Helsinki, 00290, Helsinki, Finland;Blueprint Genetics, Helsinki, Finland;Hospital for Children and Adolescents, Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland;Blueprint Genetics, Helsinki, Finland;Institute of Biomedicine, University of Helsinki, Helsinki, Finland;Department of Cardiology, Päijät-Häme Central Hospital, Lahti, Finland;Department of Clinical Physiology and Nuclear Medicine, HUS Medical Imaging Center, Helsinki University Hospital and University of Helsinki, 00290, Helsinki, Finland;Heart and Lung Center HUH, University of Helsinki, Helsinki, Finland;

关键词: Arrhythmogenic right ventricular cardiomyopathy;    Cardiomyopathies;    Desmosomes;    DSG2;    Mutation;    Case series;   

DOI  :  10.1186/s12881-017-0442-3

 received in 2017-01-03, accepted in 2017-07-13,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundArrhythmogenic 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 presentationWe 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© The Author(s). 2017