title: Whole-exome sequencing identifies MYO15A mutations as a cause of autosomal recessive nonsyndromic hearing loss in Korean families.
abstract: BACKGROUND
  The genetic heterogeneity of hearing loss makes genetic diagnosis expensive and time consuming using available methods. Whole-exome sequencing has recently been introduced as an alternative approach to identifying causative mutations in Mendelian disorders.
  
  
  METHODS
  To identify the hidden mutations that cause autosomal recessive nonsyndromic hearing loss (ARNSHL), we performed whole-exome sequencing of 13 unrelated Korean small families with ARNSHL who were negative for GJB2 or SLC26A4 mutations.
  
  
  RESULTS
  We found two novel compound heterozygous mutations, IVS11 + 1 and p.R2146Q, of MYO15A in one (SR903 family) of the 13 families with ARNSHL. In addition to these causative mutations, 13 nonsynonymous variants, including variants with uncertain pathogenicity (SR285 family), were identified in the coding exons of MYO15A from Korean exomes.
  
  
  CONCLUSIONS
  This is the first report of MYO15A mutations in an East Asian population. We suggest that close attention should be paid to this gene when performing genetic testing of patients with hearing loss in East Asia. The present results also indicate that whole-exome sequencing is a valuable method for comprehensive medical diagnosis of a genetically heterogeneous recessive disease, especially in small-sized families.
authors.affiliation: Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do 363-951, South Korea.
authors.forename: Hae-Mi
authors.initials: HM
authors.lastname: Woo
authors.forename: Hong-Joon
authors.initials: HJ
authors.lastname: Park
authors.forename: Jeong-In
authors.initials: JI
authors.lastname: Baek
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Park
authors.forename: Un-Kyung
authors.initials: UK
authors.lastname: Kim
authors.forename: Borum
authors.initials: B
authors.lastname: Sagong
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Koo
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002869:Chromosome Aberrations; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D059472:Exome / Q000235:genetics*; D005808:Genes, Recessive; D005820:Genetic Testing; D014644:Genetic Variation; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D009154:Mutation; D009218:Myosins / Q000235:genetics*; D056910:Republic of Korea; D017422:Sequence Analysis, DNA; D000076988:Sulfate Transporters
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; C485245:MYO15A protein, human; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26; D009218:Myosins