title: A novel missense mutation in a C2 domain of OTOF results in autosomal recessive auditory neuropathy.
abstract: Screening of 12 Turkish families with apparently autosomal recessive nonsyndromic sensorineural deafness without GJB2 and mtDNA m.1555A > G mutations for 11 previously mapped recessive deafness loci showed a family in which hearing loss cosegregated with the DFNB9 (OTOF) locus. Three affected children were later found to carry a novel homozygous c.3032T > C (p.Leu1011Pro) mutation in the OTOF gene. Both parents were heterozygous for the mutation. p.Leu1011Pro alters a conserved leucine residue in the C2D domain of otoferlin. Pure tone audiometry of the family showed severe to profound sensorineural hearing loss (with U-shape audiograms) in children, and normal hearing in the parents. Otoacoustic emissions and auditory brainstem response (ABR) suggested the presence of auditory neuropathy in affected individuals.
authors.affiliation: Division of Pediatric Molecular Genetics, Ankara University School of Medicine, Ankara, Turkey. mtekin@medicine.ankara.edu.tr
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
authors.forename: Duygu
authors.initials: D
authors.lastname: Akcayoz
authors.forename: Armagan
authors.initials: A
authors.lastname: Incesulu
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002648:Child; D000072259:Connexin 26; D017630:Connexins; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017386:Sequence Homology, Amino Acid; D014421:Turkey
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D008565:Membrane Proteins; C118457:OTOF protein, human; D000072259:Connexin 26