title: OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele.
abstract: BACKGROUND
  The majority of hearing loss in children can be accounted for by genetic causes. Non-syndromic hearing loss accounts for 80% of genetic hearing loss in children, with mutations in DFNB1/GJB2 being by far the most common cause. Among the second tier genetic causes of hearing loss in children are mutations in the DFNB9/OTOF gene.
  
  
  METHODS
  In total, 65 recessive non-syndromic hearing loss families were screened by genotyping for association with the DFNB9/OTOF gene. Families with genotypes consistent with linkage or uninformative for linkage to this gene region were further screened for mutations in the 48 known coding exons of otoferlin.
  
  
  RESULTS
  Eight OTOF pathological variants were discovered in six families. Of these, Q829X was found in two families. We also noted 23 other coding variant, believed to have no pathology. A previously published missense allele I515T was found in the heterozygous state in an individual who was observed to be temperature sensitive for the auditory neuropathy phenotype.
  
  
  CONCLUSIONS
  Mutations in OTOF cause both profound hearing loss and a type of hearing loss where otoacoustic emissions are spared called auditory neuropathy.
authors.affiliation: Center for Hereditary Communication Disorders, Boys Town National Research Hospital (BTNRH), Omaha, NE, USA.
authors.forename: R
authors.initials: R
authors.lastname: Varga
authors.forename: M R
authors.initials: MR
authors.lastname: Avenarius
authors.forename: P M
authors.initials: PM
authors.lastname: Kelley
authors.forename: B J
authors.initials: BJ
authors.lastname: Keats
authors.forename: C I
authors.initials: CI
authors.lastname: Berlin
authors.forename: L J
authors.initials: LJ
authors.lastname: Hood
authors.forename: T G
authors.initials: TG
authors.lastname: Morlet
authors.forename: S M
authors.initials: SM
authors.lastname: Brashears
authors.forename: A
authors.initials: A
authors.lastname: Starr
authors.forename: E S
authors.initials: ES
authors.lastname: Cohn
authors.forename: R J H
authors.initials: RJ
authors.lastname: Smith
authors.forename: W J
authors.initials: WJ
authors.lastname: Kimberling
mesh_terms: D002648:Child; D002874:Chromosome Mapping; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005190:Family; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D008565:Membrane Proteins; C118457:OTOF protein, human; D000072259:Connexin 26