Genes, Vol. 10, Pages 918: Restrictive Cardiomyopathy is Caused by a Novel Homozygous Desmin (DES) Mutation p.Y122H Leading to a Severe Filament Assembly Defect
Genes, Vol. 10, Pages 918: Restrictive Cardiomyopathy is Caused by a Novel Homozygous Desmin (DES) Mutation p.Y122H Leading to a Severe Filament Assembly Defect
Genes doi: 10.3390/genes10110918
Authors:
Andreas Brodehl
Seyed Ahmad Pour Hakimi
Caroline Stanasiuk
Sandra Ratnavadivel
Doris Hendig
Anna Gaertner
Brenda Gerull
Jan Gummert
Lech Paluszkiewicz
Hendrik Milting
Here, we present a small Iranian family, where the index patient received a diagnosis of restrictive cardiomyopathy (RCM) in combination with atrioventricular (AV) block. Genetic analysis revealed a novel homozygous missense mutation in the DES gene (c.364T > C; p.Y122H), which is absent in human population databases. The mutation is localized in the highly conserved coil-1 desmin subdomain. In silico, prediction tools indicate a deleterious effect of the desmin (DES) mutation p.Y122H. Consequently, we generated an expression plasmid encoding the mutant and wildtype desmin formed, and analyzed the filament formation in vitro in cardiomyocytes derived from induced pluripotent stem cells and HT-1080 cells. Confocal microscopy revealed a severe filament assembly defect of mutant desmin supporting the pathogenicity of the DES mutation, p.Y122H, whereas the wildtype desmin formed regular intermediate filaments. According to the guidelines of the American College of Medical Genetics and Genomics, we classified this mutation, therefore, as a novel pathogenic mutation. Our report coul...
Source: Genes - Category: Genetics & Stem Cells Authors: Andreas Brodehl Seyed Ahmad Pour Hakimi Caroline Stanasiuk Sandra Ratnavadivel Doris Hendig Anna Gaertner Brenda Gerull Jan Gummert Lech Paluszkiewicz Hendrik Milting Tags: Article Source Type: research
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