Article

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

Department of Hearing and Speech Sciences, Vanderbilt University, Нашвилл, Michigan, United States
Journal of Medical Genetics (Impact Factor: 5.64). 08/2006; 43(7):576-81. DOI: 10.1136/jmg.2005.038612
Source: PubMed

ABSTRACT 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.
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.
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.
Mutations in OTOF cause both profound hearing loss and a type of hearing loss where otoacoustic emissions are spared called auditory neuropathy.

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    • "on mice lacking VGLUT3 support that hypothesis. This neurotransmitter hypothesis was clinically supported by the genetic research that showed that ANSD in some children is due to mutation in the otoferlin gene (OTOF) [37]. Otoferlin is expressed in the IHCs and it is essential for the process of neurotransmitter release; therefore otoferlin deficiency leaves the IHC/synapse not functioning and leads to the clinical manifestations of ANSD [38]. "
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