Nature Genetics
20, 299 - 303 (1998)
doi:10.1038/3118
Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic
deafness with vestibular dysfunctionNahid G. Robertson1, 8, Leonard Lu2, 8, Stefan Heller3, Saumil N. Merchant4, Roland D. Eavey4, Michael McKenna4, Joseph B. Nadol Jr4, Richard T. Miyamoto5, Frederick H. Linthicum Jr6, José F. Lubianca Neto4, A.J. Hudspeth3, Christine E. Seidman7, Cynthia C. Morton1, 8
& J.G. Seidman2, 81
Departments of Pathology, Obstetrics, Gynecology and
Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115,
USA. 2
Department of Genetics and the Howard Hughes Medical
Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. 3
Laboratory of Sensory Neuroscience and the Howard Hughes
Medical Institute, The Rockefeller University, New York,
New York 10021, USA. 4
Department of Otolaryngology, Massachusetts Eye and
Ear Infirmary and Otology and Laryngology, Harvard Medical School,
Boston, Massachusetts 02114, USA. 5
Department of Otolaryngology, Indiana University School
of Medicine, Indianapolis, Indiana 46202,
USA. 6
Department of Histopathology, House Ear Institute,
Los Angeles, California 90057, USA. 7
Department of Medicine and the Howard Hughes Medical
Institute, Brigham and Women's Hospital, Harvard Medical School,
Boston, Massachusetts 02115, USA. 8
These authors contributed equally to this work.
Correspondence should be addressed to Cynthia C. Morton ccmorton@bics.bwh.harvard.eduDFNA9 is an autosomal dominant, nonsyndromic, progressive sensorineural
hearing loss with vestibular pathology. Here we report three missense mutations
in human COCH (previously described as Coch5b2), a novel cochlear
gene, in three unrelated kindreds with DFNA9. All three residues mutated in
DFNA9 are conserved in mouse and chicken Coch, and are found in a region
containing four conserved cysteines with homology to a domain in factor C,
a lipopolysaccharide-binding coagulation factor in Limulus polyphemus. COCH message, found at high levels in human cochlear and vestibular organs,
occurs in the chicken inner ear in the regions of the auditory and vestibular
nerve fibres, the neural and abneural limbs adjacent to the cochlear sensory
epithelium and the stroma of the crista ampullaris of the vestibular labyrinth.
These areas correspond to human inner ear structures which show histopathological
findings of acidophilic ground substance in DFNA9 patients.
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