title: Whole exome sequencing identifies a novel EMD mutation in a Chinese family with dilated cardiomyopathy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Mingqiu
authors.initials: M
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.forename: Dayong
authors.initials: D
authors.lastname: Si
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.forename: Haixu
authors.initials: H
authors.lastname: Jiao
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Feng
authors.affiliation: State Key Lab of Medical Genetics, Central South University, 410008 Changsha, Hunan province, China. huzhengmao@sklmg.edu.cn.
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.forename: Ranhui
authors.initials: R
authors.lastname: Duan
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D002681:China; D059472:Exome; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
chemical_list: C509754:GPR50 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D043562:Receptors, G-Protein-Coupled; C092710:emerin