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.
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.
Authors: T J Keen; C F Inglehearn; E D Green; A F Cunningham; R J Patel; R E Peacock; S Gerken; R White; J Weissenbach; S S Bhattacharya Journal: Genomics Date: 1995-08-10 Impact factor: 5.736
Authors: G Rance; D E Beer; B Cone-Wesson; R K Shepherd; R C Dowell; A M King; F W Rickards; G M Clark Journal: Ear Hear Date: 1999-06 Impact factor: 3.570
Authors: S Yasunaga; M Grati; M Cohen-Salmon; A El-Amraoui; M Mustapha; N Salem; E El-Zir; J Loiselet; C Petit Journal: Nat Genet Date: 1999-04 Impact factor: 38.330
Authors: T Moser; N Strenzke; A Meyer; A Lesinski-Schiedat; T Lenarz; D Beutner; A Foerst; R Lang-Roth; H von Wedel; M Walger; M Gross; A Keilmann; A Limberger; T Steffens; J Strutz Journal: HNO Date: 2006-11 Impact factor: 1.284
Authors: Monica Uddin; Allison E Aiello; Derek E Wildman; Karestan C Koenen; Graham Pawelec; Regina de Los Santos; Emily Goldmann; Sandro Galea Journal: Proc Natl Acad Sci U S A Date: 2010-05-03 Impact factor: 11.205
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