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.
- ABR, auditory brainstem responses
- AD, auditory dys-synchrony
- AN, auditory neuropathy
- AR, acoustic reflexes
- CM, cochlear microphonics
- DHPLC, denaturing high performance liquid chromatography
- HL, hearing loss
- IHC, inner hair cells
- MDE, mutation detection enhancement
- MOC, medial olivocochlear
- NSRAN, non-syndromic recessive auditory neuropathy
- NSRHL, non-syndromic recessive hearing loss
- OAE, otoacoustic emissions
- OHC, outer hair cell
- SAT, speech awareness threshold
- SSCP, single strand conformational polymorphism
- SRT, speech reception threshold
- auditory neuropathy
- hearing loss
- temperature sensitive
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