title: Whole-Exome Sequencing Identifies Two Novel TTN Mutations in Chinese Families with Dilated Cardiomyopathy.
abstract: OBJECTIVE
  Dilated cardiomyopathy (DCM) is a leading cause of sudden cardiac death. So far, only 127 mutations of Titin(TTN) have been reported in patients with different phenotypes such as isolated cardiomyopathies, purely skeletal muscle phenotypes or complex overlapping disorders of muscles.
  
  
  METHODS
  We applied whole-exome sequencing (WES) to investigate cardiomyopathy patients and a cardiomyopathy-related gene-filtering strategy was used to analyze the disease-causing mutations. Sanger sequencing was applied to confirm the mutation cosegregation in the affected families.
  
  
  RESULTS
  A nonsense mutation (c.12325C>T/p.R4109X) and a missense mutation (c.17755G>C/p.G5919R) of TTN were identified in 2 Chinese DCM families, respectively. Both mutations were cosegregated in all affected members of both families. The nonsense mutation is predicted to result in a truncated TTN protein and the missense mutation leads to a substitution of glycine by arginine. Both variants may cause the structure changes of titin protein.
  
  
  CONCLUSIONS
  We employed WES to detect the mutations of DCM patients and identified 2 novel mutations. Our study expands the spectrum of TTN mutations and offers accurate genetic testing information for DCM patients who are still clinically negative.
authors.affiliation: The State Key Laboratory of Medical Genetics and School of Life Sciences, Central South University, Changsha, China.
authors.forename: Ji-Shi
authors.initials: JS
authors.lastname: Liu
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: Fan
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiaoxian
authors.initials: X
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.forename: Li-Jian
authors.initials: LJ
authors.lastname: Tao
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000235:genetics*; D002681:China; D018389:Codon, Nonsense; D064211:Connectin / Q000235:genetics*; D004252:DNA Mutational Analysis; D004452:Echocardiography; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D000073359:Exome Sequencing; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D064211:Connectin; C577285:TTN protein, human