Nature Genetics
23, 413 - 419 (1999)
doi:10.1038/70516
Mutations in COL11A2 cause non-syndromic hearing loss (DFNA13)
Wyman T. McGuirt1, Sai D. Prasad1, Andrew J. Griffith2, Henricus P.M. Kunst3, Glenn E. Green1, Karl B. Shpargel2, Christina Runge1, Christy Huybrechts4, Robert F. Mueller5, Eric Lynch6, Mary-Claire King6, Han G. Brunner3, Cor W.R.J. Cremers3, Masamine Takanosu7, Shi-Wu Li8, Machiko Arita8, Richard Mayne7, Darwin J. Prockop8, Guy Van Camp4
& Richard J.H. Smith11
Molecular Otolaryngology Research Laboratories, Department
of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa
City, Iowa, USA. 2
National Institute on Deafness and Other Communication
Disorders, National Institutes of Health, Bethesda,
Maryland, USA. 3
Department of Otorhinolaryngology, University Hospital
, Nijmegen, The Netherlands. 4
Department of Genetics, University of Antwerp,
Belgium. 5
Department of Clinical Genetics, St James's Hospital
, Leeds, UK. 6
Department of Medicine, University of Washington,
Seattle, Washington, USA. 7
Department of Cell Biology, University of Alabama at
Birmingham, Birmingham, Alabama, USA.
8
Center for Gene Therapy, MCP Hahnemann University School
of Medicine, Philadelphia, Pennsylvania, USA
.
Correspondence should be addressed to Richard J.H. Smith richard-smith@uiowa.eduWe 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.
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