title: A prevalent founder mutation and genotype-phenotype correlations of OTOF in Japanese patients with auditory neuropathy.
abstract: Auditory neuropathy is a hearing disorder characterized by normal outer hair cell function and abnormal neural conduction of the auditory pathway. Aetiology and clinical presentation of congenital or early-onset auditory neuropathy are heterogeneous, and their correlations are not well understood. Genetic backgrounds and associated phenotypes of congenital or early-onset auditory neuropathy were investigated by systematically screening a cohort of 23 patients from unrelated Japanese families. Of the 23 patients, 13 (56.5%) had biallelic mutations in OTOF, whereas little or no association was detected with GJB2 or PJVK, respectively. Nine different mutations of OTOF were detected, and seven of them were novel. p.R1939Q, which was previously reported in one family in the United States, was found in 13 of the 23 patients (56.5%), and a founder effect was determined for this mutation. p.R1939Q homozygotes and compound heterozygotes of p.R1939Q and truncating mutations or a putative splice site mutation presented with stable, and severe-to-profound hearing loss with a flat or gently sloping audiogram, whereas patients who had non-truncating mutations except for p.R1939Q presented with moderate hearing loss with a steeply sloping, gently sloping or flat audiogram, or temperature-sensitive auditory neuropathy. These results support the clinical significance of comprehensive mutation screening for auditory neuropathy.
authors.affiliation: Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsunaga
authors.forename: H
authors.initials: H
authors.lastname: Mutai
authors.forename: S
authors.initials: S
authors.lastname: Kunishima
authors.forename: K
authors.initials: K
authors.lastname: Namba
authors.forename: N
authors.initials: N
authors.lastname: Morimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Shinjo
authors.forename: Y
authors.initials: Y
authors.lastname: Arimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kataoka
authors.forename: T
authors.initials: T
authors.lastname: Shintani
authors.forename: N
authors.initials: N
authors.lastname: Morita
authors.forename: T
authors.initials: T
authors.lastname: Sugiuchi
authors.forename: S
authors.initials: S
authors.lastname: Masuda
authors.forename: A
authors.initials: A
authors.lastname: Nakano
authors.forename: H
authors.initials: H
authors.lastname: Taiji
authors.forename: K
authors.initials: K
authors.lastname: Kaga
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018703:Founder Effect; D056726:Genetic Association Studies / Q000379:methods*; D005820:Genetic Testing; D005838:Genotype; D006313:Hearing Loss, Central / Q000453:epidemiology* / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D015995:Prevalence; D011487:Protein Conformation; D017422:Sequence Analysis, DNA; D000094524:Gasdermins
chemical_list: D000072259:Connexin 26; D017630:Connexins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C000607042:GJB2 protein, human; C118457:OTOF protein, human; C519847:PJVK protein, human; D000094524:Gasdermins