TY - JOUR T1 - OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele JF - Journal of Medical Genetics JO - J Med Genet SP - 576 LP - 581 DO - 10.1136/jmg.2005.038612 VL - 43 IS - 7 AU - R Varga AU - M R Avenarius AU - P M Kelley AU - B J Keats AU - C I Berlin AU - L J Hood AU - T G Morlet AU - S M Brashears AU - A Starr AU - E S Cohn AU - R J H Smith AU - W J Kimberling Y1 - 2006/07/01 UR - http://jmg.bmj.com/content/43/7/576.abstract N2 - 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. ER -