This is a report of the audiological and vestibular characteristics of a Dutch DFNA9 family with a novel mutation, I109T, in the LCCL domain of COCH.
Methods:
From the family with the novel I109T COCH mutation, audiometric data were collected and analyzed longitudinally. Results were compared to those obtained in previously identified P51S, G88E, and G87W COCH mutation carriers. Special attention was also given to a comparison of age-related features such as progressive hearing loss and vestibular impairment.
Results:
A novel mutation (I109T) in COCH segregates with hearing impairment and vestibular dysfunction in the present family. Pure tone thresholds, phoneme recognition scores, and vestibular responses of the I109T mutation carriers were essentially similar to those previously established in P51S, G87W, and G88E mutation carriers. Deterioration of hearing in the I109T mutation carriers started at 43 years of age, and vestibular function deteriorated at least 7 years later.
Conclusions:
The phenotype associated with the novel COCH (I109T) mutation is largely similar to that associated with P51S and G88E mutation carriers. However, subtle differences in terms of onset age and rate of progression seem to exist.
BomSJHKempermanMHDe KokYJ. Progressive cochleovestibular impairment caused by a point mutation in the COCH gene at DFNA9. Laryngoscope1999;109:1525–30.
3.
de KokYJBomSJHBruntTM. A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects. Hum Mol Genet1999;8:361–6.
4.
BischoffAMLCHuygenPLMKempermanMH. Vestibular deterioration precedes hearing deterioration in the P51S COCH mutation (DFNA9): An analysis in 74 mutation carriers. Otol Neurotol2005;26:918–25.
5.
VerhagenWIMBomSJHFransenE. Hereditary cochleovestibular dysfunction due to a COCH gene mutation (DFNA9): A follow-up study of a family. Clin Otolaryngol Allied Sci2001;26:477–83.
6.
LemaireFXFeenstraLHuygenPLM. Progressive late-onset sensorineural hearing loss and vestibular impairment with vertigo (DFNA9/COCH): Longitudinal analyses in a Belgian family. Otol Neurotol2003;24:743–8.
7.
ManolisENYandaviNNadolJBJr. A gene for non-syndromic autosomal dominant progressive postlingual sensorineural hearing loss maps to chromosome 14q12–13. Hum Mol Genet1996;5:1047–50.
8.
RobertsonNGLuLHellerS. Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction. Nat Genet1998;20:299–303.
9.
FransenEVerstrekenMVerhagenWI. High prevalence of symptoms of Meniere's disease in three families with a mutation in the COCH gene. Hum Mol Genet1999;8:1425–9.
10.
RobertsonNGResendesBLLinJS. Inner ear localization of mRNA and protein products of COCH, mutated in the sensorineural deafness and vestibular disorder, DFNA9. Hum Mol Genet2001;10:2493–500.
11.
UsamiSTakahashiKYugeI. Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease. Eur J Hum Genet2003;11:744–8.
12.
NagyIHorvathMTrexlerMRepassyGPatthyL. A novel COCH mutation, V104del, impairs folding of the LCCL domain of cochlin and causes progressive hearing loss. J Med Genet2004;41:e9.
13.
CollinRWJPauwRJSchootsJ. Identification of a novel COCH mutation, G87W, causing autosomal dominant hearing impairment (DFNA9). Am J Med Genet A2006;140:1791–4.
14.
KamarinosMMcGillJLynchMDahlH. Identification of a novel COCH mutation, I109N, highlights the similar clinical features observed in DFNA9 families. Hum Mutat2001;17:351. [Erratum in Hum Mutat 2001;18:547–8.]
15.
StreetVAKallmanJCRobertsonNGKuoSFMortonCCPhillipsJO. A novel DFNA9 mutation in the vWFA2 domain of COCH alters a conserved cysteine residue and intrachain disulfide bond formation resulting in progressive hearing loss and site-specific vestibular and central oculomotor dysfunction. Am J Med Genet A2005;139:86–95.
16.
LiepinshETrexlerMKaikkonenA. NMR structure of the LCCL domain and implications for DFNA9 deafness disorder. EMBO J2001;20:5347–53.
17.
KhetarpalU. Autosomal dominant sensorineural hearing loss. Further temporal bone findings. Arch Otolaryngol Head Neck Surg1993;119:106–8.
18.
KhetarpalUSchuknechtHFGacekRRHolmesLB. Autosomal dominant sensorineural hearing loss. Pedigrees, audiologic findings, and temporal bone findings in two kindreds. Arch Otolaryngol Head Neck Surg1991;117:1032–42.
19.
RobertsonNGCremersCWHuygenPL. Cochlin immunostaining of inner ear pathologic deposits and proteomic analysis in DFNA9 deafness and vestibular dysfunction. Hum Mol Genet2006;15:1071–85.
20.
BischoffAMLCPauwRJHuygenPLM. Vertical corneal striae in families with autosomal dominant hearing loss: DFNA9/COCH. Am J Ophthalmol (in press).
21.
International Organization for Standardization. ISO 7029. Acoustics: Threshold of hearing by air conduction as a function of age and sex for otologically normal persons. Geneva, Switzerland: International Organization for Standardization, 1984.
22.
HuygenPLMPenningsRJECremersCWRJ. Characterizing and distinguishing progressive phenotypes in nonsyndromic autosomal dominant hearing impairment. Audiol Med2003;1:37–46.
23.
BomSJHDe LeenheerEMRLemaireFX. Speech recognition scores related to age and degree of hearing impairment in DFNA2/KCNQ4 and DFNA9/COCH. Arch Otolaryngol Head Neck Surg2001;127:1045–8.
24.
De LeenheerEMRHuygenPLMCouckePJAdmiraalRJCvan CampGCremersCWRJ. Longitudinal and cross-sectional phenotype analysis in a new, large Dutch DFNA2/KCNQ4 family. Ann Otol Rhinol Laryngol2002;111:267–74.
25.
KunstHPMHuybrechtsCMarresHAMHuygenPLMVan CampGCremersCWRJ. The phenotype of DFNA13/COL11A2: Nonsyndromic autosomal dominant mid-frequency and high-frequency sensorineural hearing impairment. Am J Otol2000;21:181–7.
26.
TheunissenEJJMHuygenPLMFolgeringHT. Vestibular hyperreactivity and hyperventilation. Clin Otolaryngol Allied Sci1986;11:161–9.
27.
KempermanMHDe LeenheerEMRHuygenPLM. Audiometric, vestibular, and genetic aspects of a DFNA9 family with a G88E COCH mutation. Otol Neurotol2005;26:926–33.
28.
PauwRJCollinRWJHuygenPLMHoefslootLHKremerHCremersCWRJ. Clinical characteristics of a Dutch DFNA9 family with a novel COCH mutation, G87W. Audiol Neurootol2007;12:77–84.
