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: T Matsunaga, H Mutai, S Kunishima, K Namba, N Morimoto, Y Shinjo, Y Arimoto, Y Kataoka, T Shintani, N Morita, T Sugiuchi, S Masuda, A Nakano, H Taiji, K Kaga
• Journal: Clinical genetics (Clin Genet) Vol. 82 Issue 5 Pg. 425-32 (Nov 2012) ISSN: 1399-0004 [Electronic] Denmark
• PMID: 22575033 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 John Wiley & Sons A/S.

Chemical References

• Connexins
• GJB2 protein, human
• Membrane Proteins
• Nerve Tissue Proteins
• OTOF protein, human
• PJVK protein, human
• Connexin 26

Topics

• Adult
• Amino Acid Sequence
• Asian People (genetics)
• Child
• Child, Preschool
• Connexin 26
• Connexins (genetics, metabolism)
• Female
• Founder Effect
• Genetic Association Studies (methods)
• Genetic Testing
• Genotype
• Hearing Loss, Central (epidemiology, genetics)
• Heterozygote
• Homozygote
• Humans
• Infant
• Male
• Membrane Proteins (genetics)
• Molecular Sequence Data
• Mutation
• Nerve Tissue Proteins (genetics, metabolism)
• Phenotype
• Prevalence
• Protein Conformation
• Sequence Analysis, DNA