Mutations in COL11A2 cause non-syndromic hearing loss (DFNA13). Nat Genet 1999 Dec;23(4):413-9
Date
12/02/1999Pubmed ID
10581026DOI
10.1038/70516Scopus ID
2-s2.0-0032755733 (requires institutional sign-in at Scopus site) 202 CitationsAbstract
We report that mutation of COL11A2 causes deafness previously mapped to the DFNA13 locus on chromosome 6p. We found two families (one American and one Dutch) with autosomal dominant, non-syndromic hearing loss to have mutations in COL11A2 that are predicted to affect the triple-helix domain of the collagen protein. In both families, deafness is non-progressive and predominantly affects middle frequencies. Mice with a targeted disruption of Col11a2 also were shown to have hearing loss. Electron microscopy of the tectorial membrane of these mice revealed loss of organization of the collagen fibrils. Our findings revealed a unique ultrastructural malformation of inner-ear architecture associated with non-syndromic hearing loss, and suggest that tectorial membrane abnormalities may be one aetiology of sensorineural hearing loss primarily affecting the mid-frequencies.
Author List
McGuirt WT, Prasad SD, Griffith AJ, Kunst HP, Green GE, Shpargel KB, Runge C, Huybrechts C, Mueller RF, Lynch E, King MC, Brunner HG, Cremers CW, Takanosu M, Li SW, Arita M, Mayne R, Prockop DJ, Van Camp G, Smith RJAuthor
Christina Runge PhD Associate Provost, Chief, Professor in the Otolaryngology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Base Sequence
Chromosomes, Human, Pair 6
Collagen
DNA
Disease Models, Animal
Female
Genes, Dominant
Hearing Loss, Sensorineural
Humans
In Situ Hybridization
Male
Mice
Mice, Knockout
Molecular Sequence Data
Mutation, Missense
Pedigree
Polymorphism, Single-Stranded Conformational
