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Kostareva, A.* ; Kiselev, A.* ; Gudkova, A.* ; Frishman, G. ; Ruepp, A. ; Frishman, D. ; Smolina, N.* ; Tarnovskaya, S.* ; Nilsson, D.* ; Zlotina, A.* ; Khodyuchenko, T.* ; Vershinina, T.* ; Pervunina, T.* ; Klyushina, A.* ; Kozlenok, A.* ; Sjoberg, G.* ; Golovljova, I.* ; Sejersen, T.* ; Shlyakhto, E.*

Genetic spectrum of idiopathic restrictive cardiomyopathy uncovered by next-generation sequencing.

PLoS ONE 11:e0163362 (2016)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: Cardiomyopathies represent a rare group of disorders often of genetic origin. While approximately 50% of genetic causes are known for other types of cardiomyopathies, the genetic spectrum of restrictive cardiomyopathy (RCM) is largely unknown. The aim of the present study was to identify the genetic background of idiopathic RCM and to compile the obtained genetic variants to the novel signalling pathways using in silico protein network analysis. PATIENTS AND METHODS: We used Illumina MiSeq setup to screen for 108 cardiomyopathy and arrhythmia-associated genes in 24 patients with idiopathic RCM. Pathogenicity of genetic variants was classified according to American College of Medical Genetics and Genomics classification. RESULTS: Pathogenic and likely-pathogenic variants were detected in 13 of 24 patients resulting in an overall genotype-positive rate of 54%. Half of the genotype-positive patients carried a combination of pathogenic, likely-pathogenic variants and variants of unknown significance. The most frequent combination included mutations in sarcomeric and cytoskeletal genes (38%). A bioinformatics approach underlined the mechanotransducing protein networks important for RCM pathogenesis. CONCLUSIONS: Multiple gene mutations were detected in half of the RCM cases, with a combination of sarcomeric and cytoskeletal gene mutations being the most common. Mutations of genes encoding sarcomeric, cytoskeletal, and Z-line-associated proteins appear to have a predominant role in the development of RCM.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Familial Hypertrophic Cardiomyopathy; Sarcomere Protein Genes; Dilated Cardiomyopathy; Mutations; Disease; Organization; Annotations; Database; Defects; Society
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 11, Issue: 9, Pages: , Article Number: e0163362 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Bioinformatics and Systems Biology (IBIS)