OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele

R. Varga, M. R. Avenarius, Philip M Kelley, B. J. Keats, C. I. Berlin, L. J. Hood, T. G. Morlet, S. M. Brashears, A. Starr, E. S. Cohn, R. J.H. Smith, William J Kimberling

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Abstract

Introduction: 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.

Original languageEnglish (US)
Pages (from-to)576-581
Number of pages6
JournalJournal of medical genetics
Volume43
Issue number7
DOIs
StatePublished - Jul 1 2006

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Hearing Loss
Alleles
Mutation
Temperature
Genes
Auditory neuropathy
Exons
Genotype
Pathology
Phenotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele. / Varga, R.; Avenarius, M. R.; Kelley, Philip M; Keats, B. J.; Berlin, C. I.; Hood, L. J.; Morlet, T. G.; Brashears, S. M.; Starr, A.; Cohn, E. S.; Smith, R. J.H.; Kimberling, William J.

In: Journal of medical genetics, Vol. 43, No. 7, 01.07.2006, p. 576-581.

Research output: Contribution to journalArticle

Varga, R, Avenarius, MR, Kelley, PM, Keats, BJ, Berlin, CI, Hood, LJ, Morlet, TG, Brashears, SM, Starr, A, Cohn, ES, Smith, RJH & Kimberling, WJ 2006, 'OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele', Journal of medical genetics, vol. 43, no. 7, pp. 576-581. https://doi.org/10.1136/jmg.2005.038612
Varga, R. ; Avenarius, M. R. ; Kelley, Philip M ; Keats, B. J. ; Berlin, C. I. ; Hood, L. J. ; Morlet, T. G. ; Brashears, S. M. ; Starr, A. ; Cohn, E. S. ; Smith, R. J.H. ; Kimberling, William J. / OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele. In: Journal of medical genetics. 2006 ; Vol. 43, No. 7. pp. 576-581.
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