title: Targeted exome sequencing reveals novel USH2A mutations in Chinese patients with simplex Usher syndrome.
abstract: BACKGROUND
  Usher syndrome (USH) is an autosomal recessive disorder characterized by hearing impairment and vision dysfunction due to retinitis pigmentosa. Phenotypic and genetic heterogeneities of this disease make it impractical to obtain a genetic diagnosis by conventional Sanger sequencing.
  
  
  METHODS
  In this study, we applied a next-generation sequencing approach to detect genetic abnormalities in patients with USH. Two unrelated Chinese families were recruited, consisting of two USH afflicted patients and four unaffected relatives. We selected 199 genes related to inherited retinal diseases as targets for deep exome sequencing. Through systematic data analysis using an established bioinformatics pipeline, all variants that passed filter criteria were validated by Sanger sequencing and co-segregation analysis.
  
  
  RESULTS
  A homozygous frameshift mutation (c.4382delA, p.T1462Lfs*2) was revealed in exon20 of gene USH2A in the F1 family. Two compound heterozygous mutations, IVS47 + 1G > A and c.13156A > T (p.I4386F), located in intron 48 and exon 63 respectively, of USH2A, were identified as causative mutations for the F2 family. Of note, the missense mutation c.13156A > T has not been reported so far.
  
  
  CONCLUSIONS
  In conclusion, targeted exome sequencing precisely and rapidly identified the genetic defects in two Chinese USH families and this technique can be applied as a routine examination for these disorders with significant clinical and genetic heterogeneity.
authors.affiliation: Department of Otolaryngology, Taizhou Central Hospital, Taizhou University School of Medicine, No 999, Donghai Rd., Taizhou, Zhejiang, 318000, China. drshu@126.com.
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Shu
authors.affiliation: Department of Otolaryngology, Taihe People's Hospital, No 158, Shengli Rd., Taihe, Jiangxi, 343700, China.
authors.forename: Huai
authors.initials: H
authors.lastname: Bi
authors.affiliation: Department of Otolaryngology, the Forth Affiliated Hospital of Shihezi University School of Medicine, Beier Rd., Shihezi, Xinjiang, 843000, China.
authors.forename: Yang-Chun
authors.initials: YC
authors.lastname: Pan
authors.affiliation: Department of Otolaryngology, Taizhou Central Hospital, Taizhou University School of Medicine, No 999, Donghai Rd., Taizhou, Zhejiang, 318000, China.
authors.forename: Hang-Yu
authors.initials: HY
authors.lastname: Xu
authors.affiliation: Department of Otolaryngology, Taizhou Central Hospital, Taizhou University School of Medicine, No 999, Donghai Rd., Taizhou, Zhejiang, 318000, China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Song
authors.affiliation: Department of Ophthalmology, Taizhou Central Hospital, Taizhou University School of Medicine, No 999, Donghai Rd., Taizhou, Zhejiang, 318000, China. hujietaizhou@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D019295:Computational Biology; D059472:Exome / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D052245:Usher Syndromes / Q000235:genetics*
chemical_list: D016326:Extracellular Matrix Proteins; C112735:USH2A protein, human