title: Novel compound heterozygous mutations in MYO7A gene associated with autosomal recessive sensorineural hearing loss in a Chinese family.
abstract: OBJECTIVE
  Mutations in MYO7A gene have been reported to be associated with Usher Syndrome type 1B (USH1B) and nonsyndromic hearing loss (DFNB2, DFNA11). Most mutations in MYO7A gene caused USH1B, whereas only a few reported mutations led to DFNB2 and DFNA11. The current study was designed to investigate the mutations among a Chinese family with autosomal recessive hearing loss.
  
  
  METHODS
  In this study, we present the clinical, genetic and molecular characteristics of a Chinese family. Targeted capture of 127 known deafness genes and next-generation sequencing were employed to study the genetic causes of two siblings in the Chinese family. Sanger sequencing was employed to examine those variant mutations in the members of this family and other ethnicity-matched controls.
  
  
  RESULTS
  We identified the novel compound heterozygous mutant alleles of MYO7A gene: a novel missense mutation c.3671C>A (p.A1224D) and a reported insert mutation c.390_391insC (p.P131PfsX9). Variants were further confirmed by Sanger sequencing. These two compound heterozygous variants were co-segregated with autosomal recessive hearing loss phenotype. The gene mutation analysis and protein sequence alignment further supported that the novel compound heterozygous mutations were pathogenic.
  
  
  CONCLUSIONS
  The novel compound heterozygous mutations (c.3671C>A and c.390_391insC) in MYO7A gene identified in this study were responsible for the autosomal recessive sensorineural hearing loss of this Chinese family.
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China; Department of Otorhinolaryngology Head and Neck Surgery, Tengzhou Central People's Hospital, Tengzhou, Shandong, PR China.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: Fengguo
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: Yuechen
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China. Electronic address: sdphxl@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China. Electronic address: sphbaixiaohui@163.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China. Electronic address: wang.hb7585@hotmail.com.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D002681:China / Q000453:epidemiology; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D016254:Mutagenesis, Insertional; D020125:Mutation, Missense; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D035781:Siblings
chemical_list: C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D009218:Myosins
keywords: Autosomal recessive inheritance; Deafness; MYO7A gene; Mutation