Audiometric, vestibular, and genetic aspects of a DFNA9 family with a G88E COCH mutation.
OBJECTIVE
To perform genetic analysis and to analyze cochleovestibular impairment features in a newly identified Dutch family with nonsyndromic autosomal dominant hearing impairment (DFNA9).


METHODS
Genetic analysis was performed using microsatellite markers and single nucleotide polymorphisms. Audiometric data were collected and analyzed longitudinally. Results were compared with those obtained in previously identified P51S COCH mutation carriers (n = 74). Special attention was also given to a comparison of age-related features such as progressive hearing loss and vestibular impairment.


METHODS
Tertiary referral center.


METHODS
G88E COCH mutation carriers from a Dutch family.


METHODS
The study of clinical features of a DFNA9 family carrying a G88E COCH mutation and to compare this to the symptoms of those carrying a P51S/COCH mutation.


RESULTS
Pure-tone thresholds, phoneme recognition scores, and vestibular responses of the G88E mutation carriers were essentially similar to those previously established in the P51S mutation carriers. Hearing started to deteriorate in G88E mutation carriers from age 46 to 49 years and onward, whereas deterioration of vestibular function started from approximately age 46 years. In the P51S mutation carriers, vestibular impairment started earlier, at approximately age 34 years. However, the difference in age of onset with the G88E mutation carriers was not significant. Remarkably, the proportion of patients who developed complete vestibular areflexia within the age range of 40 to 56 years was significantly lower for the G88E mutation carriers than for the P51S mutation carriers.


CONCLUSIONS
Apart from a significantly lower frequency of vestibular areflexia between the ages of 40 and 56 years, there are no phenotypic differences between carriers of the G88E and P51S mutations in the COCH gene.
Kemperman
Martijn H
MH
Otorhinolaryngology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands. M.Kemperman@kno.umcn.nl
De Leenheer
Els M R
EM
Huygen
Patrick L M
PL
van Duijnhoven
Gerard
G
Morton
Cynthia C
CC
Robertson
Nahid G
NG
Cremers
Frans P M
FP
Kremer
Hannie
H
Cremers
Cor W R J
CW
D000328:Adult; D000368:Aged; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold; D002883:Chromosomes, Human, Pair 14; D015834:Cochlear Diseases / Q000235:genetics*; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics*; D016326:Extracellular Matrix Proteins; D005190:Family; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D017421:Sequence Analysis
C110668:COCH protein, human; D016326:Extracellular Matrix Proteins; D011506:Proteins