Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction

Nahid G. Robertson, Leonard Lu, Stefan Heller, Saumil N. Merchant, Roland D. Eavey, Michael McKenna, Joseph B. Nadol, Richard Miyamoto, Frederick H. Linthicum, José F. Lubianca Neto, A. J. Hudspeth, Christine E. Seidman, Cynthia C. Morton, J. G. Seidman

Research output: Contribution to journalArticle

253 Citations (Scopus)

Abstract

DFNA9 is an autosomal dominant, nonsyndromic, progressive sensorineurat 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.

Original languageEnglish
Pages (from-to)299-303
Number of pages5
JournalNature Genetics
Volume20
Issue number3
DOIs
StatePublished - 1998

Fingerprint

Cochlea
Inner Ear
Mutation
Chickens
Semicircular Ducts
Labyrinth Vestibule
Vestibular Nerve
Genes
Horseshoe Crabs
Cochlear Nerve
Blood Coagulation Factors
Missense Mutation
Nerve Fibers
Hearing Loss
Cysteine
Lipopolysaccharides
Extremities
Epithelium
Pathology
Nonsyndromic Deafness

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Robertson, N. G., Lu, L., Heller, S., Merchant, S. N., Eavey, R. D., McKenna, M., ... Seidman, J. G. (1998). Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction. Nature Genetics, 20(3), 299-303. https://doi.org/10.1038/3118

Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction. / Robertson, Nahid G.; Lu, Leonard; Heller, Stefan; Merchant, Saumil N.; Eavey, Roland D.; McKenna, Michael; Nadol, Joseph B.; Miyamoto, Richard; Linthicum, Frederick H.; Lubianca Neto, José F.; Hudspeth, A. J.; Seidman, Christine E.; Morton, Cynthia C.; Seidman, J. G.

In: Nature Genetics, Vol. 20, No. 3, 1998, p. 299-303.

Research output: Contribution to journalArticle

Robertson, NG, Lu, L, Heller, S, Merchant, SN, Eavey, RD, McKenna, M, Nadol, JB, Miyamoto, R, Linthicum, FH, Lubianca Neto, JF, Hudspeth, AJ, Seidman, CE, Morton, CC & Seidman, JG 1998, 'Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction', Nature Genetics, vol. 20, no. 3, pp. 299-303. https://doi.org/10.1038/3118
Robertson, Nahid G. ; Lu, Leonard ; Heller, Stefan ; Merchant, Saumil N. ; Eavey, Roland D. ; McKenna, Michael ; Nadol, Joseph B. ; Miyamoto, Richard ; Linthicum, Frederick H. ; Lubianca Neto, José F. ; Hudspeth, A. J. ; Seidman, Christine E. ; Morton, Cynthia C. ; Seidman, J. G. / Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction. In: Nature Genetics. 1998 ; Vol. 20, No. 3. pp. 299-303.
@article{9dfe0712a6c54593a7f2353c4a9922d2,
title = "Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction",
abstract = "DFNA9 is an autosomal dominant, nonsyndromic, progressive sensorineurat 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.",
author = "Robertson, {Nahid G.} and Leonard Lu and Stefan Heller and Merchant, {Saumil N.} and Eavey, {Roland D.} and Michael McKenna and Nadol, {Joseph B.} and Richard Miyamoto and Linthicum, {Frederick H.} and {Lubianca Neto}, {Jos{\'e} F.} and Hudspeth, {A. J.} and Seidman, {Christine E.} and Morton, {Cynthia C.} and Seidman, {J. G.}",
year = "1998",
doi = "10.1038/3118",
language = "English",
volume = "20",
pages = "299--303",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction

AU - Robertson, Nahid G.

AU - Lu, Leonard

AU - Heller, Stefan

AU - Merchant, Saumil N.

AU - Eavey, Roland D.

AU - McKenna, Michael

AU - Nadol, Joseph B.

AU - Miyamoto, Richard

AU - Linthicum, Frederick H.

AU - Lubianca Neto, José F.

AU - Hudspeth, A. J.

AU - Seidman, Christine E.

AU - Morton, Cynthia C.

AU - Seidman, J. G.

PY - 1998

Y1 - 1998

N2 - DFNA9 is an autosomal dominant, nonsyndromic, progressive sensorineurat 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.

AB - DFNA9 is an autosomal dominant, nonsyndromic, progressive sensorineurat 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.

UR - http://www.scopus.com/inward/record.url?scp=17344363707&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17344363707&partnerID=8YFLogxK

U2 - 10.1038/3118

DO - 10.1038/3118

M3 - Article

VL - 20

SP - 299

EP - 303

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 3

ER -