Whole exome sequencing identifies a novel EMD mutation in a Chinese family with dilated cardiomyopathy.
Whole exome sequencing identifies a novel EMD mutation in a Chinese family with dilated cardiomyopathy.
复制标题
DOI：
10.1186/1471-2350-15-77
复制
发表时间：
2014-07-05
影响因子：
--
通讯作者：
Duan R
中科院分区：
文献类型：
--
作者：
Zhang M;Chen J;Si D;Zheng Y;Jiao H;Feng Z;Hu Z;Duan R
emerin基因（EMD）的变异与x连锁隐性emory - dreifuss肌营养不良症（EDMD）有关，其特征是早发性肌腱挛缩、进行性肌肉无力和心肌病。迄今为止，已经报道了223个EMD基因突变，其中大多数突变导致显性骨骼肌表型。在这项研究中，我们在EMD外显子1中发现了一个新的缺失突变，导致一个中国大家庭中emerin蛋白几乎完全丢失。然而，患者有严重的扩张型心肌病（DCM），但非常轻微的骨骼肌疾病。采用全外显子组测序（WES）和连锁分析鉴定了一个跨越五代的中国DCM家族的潜在突变。发现GPR50基因的错义变异与疾病表型共分离，而变体GPR50蛋白未检测到功能改变。在分析外显子组测序数据中的失败序列时，在该家族中发现了EMD外显子1中的一个新的缺失突变（c.26_39delATACCGAGCTGACC）。与大多数报道的EMD突变引起的典型临床特征不同，我们研究中的患者表现为非常轻微的骨骼肌变性，直到发现突变才被诊断出来。我们描述了一个家庭罕见的临床表现引起的一个新的EMD缺失突变。我们的发现拓宽了由EMD突变引起的表型异质性谱，并为解释EMD突变与EDMD症状之间的基因型-表型相关性提供了新的见解。
Variants in the emerin gene (EMD) were implicated in X-linked recessive Emery-Dreifuss muscular dystrophy (EDMD), characterized by early-onset contractures of tendons, progressive muscular weakness and cardiomyopathy. To date, 223 mutations have been reported in EMD gene and the majority of them caused a predominant skeletal muscular phenotype. In this study, we identified a novel deletion mutation in EMD exon 1, which results in almost a complete loss of emerin protein in a large Chinese family. However, the patients suffered severe dilated cardiomyopathy (DCM) but very mild skeletal muscle disorder. Whole exome sequencing (WES) and linkage analysis were performed to identify the underlying mutation in a Chinese DCM family spanning five generations. A missense variation in the GPR50 gene was found co-segregated with the disease phenotype, whereas no functional alteration was detected in the variant GPR50 protein. When analyzing the failure sequences in the exome sequencing data, a novel deletion mutation (c.26_39delATACCGAGCTGACC) in EMD exon 1, was identified in this family. Different from the typical clinical features caused by most reported EMD mutations, patients in our study presented very mild skeletal muscle degeneration that had not been diagnosed until the mutation was found. We described a family with rare clinical presentations caused by a novel EMD deletion mutation. Our findings broaden the heterogeneous spectrum of phenotypes attributed to EMD mutations and provide new insight to explain the genotype-phenotype correlations between EMD mutations and EDMD symptoms.