The novel B-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy

作者：Brodehl Andreas^*; Gaertner Rommel Anna; Klauke Baerbel; Grewe Simon Andre; Schirmer Ilona; Peterschroeder Andreas; Faber Lothar; Vorgerd Matthias; Gummert Jan; Anselmetti Dario; Schulz Uwe; Paluszkiewicz Lech; Milting Hendrik^*

来源：Human Mutation, 2017, 38(8): 947-952.

DOI：10.1002/humu.23248

• B-crystallin
• hypertrophic cardiomyopathy
• intermediate filaments
• restrictive cardiomyopathy
• small heat shock proteins

Restrictive cardiomyopathy (RCM) is a rare heart disease characterized by diastolic dysfunction and atrial enlargement. The genetic etiology of RCM is not completely known. We identified by a next-generation sequencing panel the novel CRYAB missense mutation c.326A>G, p.D109G in a small family with RCM in combination with skeletal myopathy with an early onset of the disease. CRYAB encodes B-crystallin, a member of the small heat shock protein family, which is highly expressed in cardiac and skeletal muscle. In addition to in silico prediction analysis, our structural analysis of explanted myocardial tissue of a mutation carrier as well as in vitro cell transfection experiments revealed abnormal protein aggregation of mutant B-crystallin and desmin, supporting the deleterious effect of this novel mutation. In conclusion, CRYAB appears to be a novel RCM gene, which might have relevance for the molecular diagnosis and the genetic counseling of further affected families in the future.

• 出版日期2017-8