TY  - JOUR
A1  - Brodehl, Andreas
A1  - Pour Hakimi, Seyed Ahmad
A1  - Stanasiuk, Caroline
A1  - Ratnavadivel, Sandra
A1  - Hendig, Doris
A1  - Gaertner, Anna
A1  - Gerull, Brenda
A1  - Gummert, Jan
A1  - Paluszkiewicz, Lech
A1  - Milting, Hendrik
T1  - Restrictive cardiomyopathy is caused by a novel homozygous desmin (DES) mutation p.Y122H leading to a severe filament assembly defect
JF  - Genes
N2  - 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 could point to a recessive inheritance of the DES mutation, p.Y122H, which is important for the genetic counseling of similar families with restrictive cardiomyopathy caused by DES mutations.
KW  - cardiovascular genetics
KW  - restrictive cardiomyopathy
KW  - desmin
KW  - intermediate filaments
KW  - desmin-related myopathy
KW  - cardiomyopathy
KW  - desminopathy
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193121
SN  - 2073-4425
VL  - 10
IS  - 11
ER  -