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

被引：60

作者：

Brodehl, Andreas ^{[1
]}

Gaertner-Rommel, Anna ^{[1
]}

Klauke, Baerbel ^{[1
]}

Grewe, Simon Andre ^{[1
]}

Schirmer, Ilona ^{[1
]}

Peterschroeder, Andreas ^{[2
]}

Faber, Lothar ^{[3
]}

Vorgerd, Matthias ^{[4
]}

Gummert, Jan ^{[1
]}

Anselmetti, Dario ^{[5
,6
]}

Schulz, Uwe ^{[1
]}

Paluszkiewicz, Lech ^{[1
]}

Milting, Hendrik ^{[1
]}

机构：

[1] Ruhr Univ Bochum, Dept Thorac & Cardiovasc Surg, Heart & Diabet Ctr NRW, Univ Hosp,Erich & Hanna Klessmann Inst Cardiovasc, Bad Oeynhausen, Germany

[2] Ruhr Univ Bochum, Dept Thorac & Cardiovasc Surg, Heart & Diabet Ctr NRW, Univ Hosp,Inst Radiol NuclearMedicine & Mol Imagi, Bad Oeynhausen, Germany

[3] Ruhr Univ Bochum, Dept Thorac & Cardiovasc Surg, Heart & Diabet Ctr NRW, Univ Hosp,Clin Cardiol, Bad Oeynhausen, Germany

[4] BG Univ Hosp Bergmannsheil, Dept Neurol, Bochum, Germany

[5] Bielefeld Univ, Bielefeld, Germany

[6] Bielefeld Inst Nanosci BINAS, Fac Phys Expt Biophys & Appl Nanosci, Bielefeld, Germany

来源：

HUMAN MUTATION | 2017年 / 38卷 / 08期

关键词：

B-crystallin; hypertrophic cardiomyopathy; intermediate filaments; restrictive cardiomyopathy; small heat shock proteins; PROTEIN AGGREGATION; GENE CAUSES; DESMIN; MYOPATHY; ASSOCIATION; TITIN;

D O I：

10.1002/humu.23248

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：947 / 952

页数：6

共 42 条

[1] Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects [J].