title: A novel splice site mutation in DFNA5 causes late-onset progressive non-syndromic hearing loss in a Chinese family.
abstract: OBJECTIVE
  Mutations in DFNA5 may lead to autosomal dominant non-syndromic sensorineural hearing loss (NSHL). To date, only four DFNA5 mutations have been reported, all resulting in skipping of exon 8 at the mRNA level. In this study, we aim to characterize the clinical features and the genetic cause of a Chinese DFNA5 family.
  
  
  METHODS
  Targeted next-generation sequencing of 79 known deafness genes was performed in the proband. Co-segregation between the disease phenotype and the potentially pathogenic variant was confirmed in all family members by Sanger sequencing.
  
  
  RESULTS
  A novel heterozygous c.991-2A>G mutation in DFNA5 was identified in this family segregating with the autosomal dominant, late-onset NSHL. This mutation was located in the conventional splice site in intron 7 and was likely to result in skipping of exon 8. The severity of hearing impairment varied intrafamilially.
  
  
  CONCLUSIONS
  We identified a novel c.991-2A>G mutation in DFNA5 which again may lead to exon 8 skipping at the mRNA level. Our findings supported that the DFNA5-associated NSHL results from a specific gain-of-function mechanism.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yongchuan
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Dongye
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: wuhao622@sina.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: yangtfxl@sina.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D002648:Child; D002681:China; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D047668:Inteins / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D012326:RNA Splicing; D011960:Receptors, Estrogen / Q000235:genetics*; D012720:Severity of Illness Index; D000094524:Gasdermins
chemical_list: D011960:Receptors, Estrogen; C111432:GSDME protein, human; D000094524:Gasdermins
keywords: Autosomal dominant hearing loss; DFNA5; Spice site mutation; Target next-generation sequencing