title: Compound heterozygous MYO7A mutations segregating Usher syndrome type 2 in a Han family.
abstract: OBJECTIVE
  Identification of rare deafness genes for inherited congenital sensorineural hearing impairment remains difficult, because a large variety of genes are implicated. In this study we applied targeted capture and next-generation sequencing to uncover the underlying gene in a three-generation Han family segregating recessive inherited hearing loss and retinitis pigmentosa.
  
  
  METHODS
  After excluding mutations in common deafness genes GJB2, SLC26A4 and the mitochondrial gene, genomic DNA of the proband of a Han family was subjected to targeted next-generation sequencing. The candidate mutations were confirmed by Sanger sequencing and subsequently analyzed with in silico tools.
  
  
  RESULTS
  An unreported splice site mutation c.3924+1G > C compound with c.6028G > A in the MYO7A gene were detected to cosegregate with the phenotype in this pedigree. Both mutations, located in the evolutionarily conserved FERM domain in myosin VIIA, were predicted to be pathogenic. In this family, profound sensorineural hearing impairment and retinitis pigmentosa without vestibular disorder, constituted the typical Usher syndrome type 2.
  
  
  CONCLUSIONS
  Identification of novel mutation in compound heterozygosity in MYO7A gene revealed the genetic origin of Usher syndrome type 2 in this Han family.
authors.affiliation: Department of Otorhinolaryngology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, PR China; Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou, 510080, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zong
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou, 510080, PR China.
authors.forename: Kaitian
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou, 510080, PR China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou, 510080, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou, 510080, PR China; Department of Otorhinolaryngology, Hainan General Hospital, Haikou, 570311, PR China. Electronic address: jhongy@mail.sysu.edu.cn.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D052245:Usher Syndromes / Q000235:genetics*; D055815:Young Adult
chemical_list: C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D009218:Myosins
keywords: Hearing; MYO7A; Nonsense-mediated mRNA decay; Targeted next-generation sequencing; Usher syndrome