The novel B-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy
The novel B-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy
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DOI：
10.1002/humu.23248
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发表时间：
2017-08-01
期刊：
影响因子：
3.9
通讯作者：
Milting, Hendrik
中科院分区：
文献类型：
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作者：
Brodehl, Andreas;Gaertner-Rommel, Anna;Milting, Hendrik
限制性心肌病（RCM）是一种罕见的心脏疾病，以舒张功能障碍和心房扩大为特征。RCM的遗传病因尚不完全清楚。我们通过下一代测序小组在一个早期发病的RCM合并骨骼肌病的小家族中发现了新的CRYAB错义突变c.326A >g, p.D109G。CRYAB编码的B-crystallin是小热休克蛋白家族的一员，在心脏和骨骼肌中高度表达。除了计算机预测分析外，我们对突变载体的外植心肌组织的结构分析以及体外细胞转染实验显示突变b -晶蛋白和desmin的异常蛋白聚集，支持这种新突变的有害作用。综上所述，CRYAB可能是一种新的RCM基因，对未来进一步患病家庭的分子诊断和遗传咨询具有重要意义。
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.