PMID- 10400989
OWN - NLM
STAT- MEDLINE
DCOM- 19990914
LR  - 20220317
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 8
DP  - 1999 Aug
TI  - High prevalence of symptoms of Meniere's disease in three families with a
      mutation in the COCH gene.
PG  - 1425-9
AB  - We report the genetic analysis of one large Belgian and two small Dutch families 
      with autosomal dominant non-syndromic progressive sensorineural hearing loss
      associated with vestibular dysfunction. Linkage studies in the Belgian family
      mapped the disease to the DFNA9 locus on chromosome 14. Mutation analysis of the 
      COCH gene, which is responsible for DFNA9, revealed a missense mutation changing 
      a highly conserved residue. One of the patients, who had an earlier age of onset 
      in comparison with most of the affected family members, was shown to be
      homozygous for the mutation. After the mutation was found in the Belgian family, 
      we discovered that the same missense mutation was also present in two Dutch
      families with similar cochleo-vestibular symptoms. In all three families with
      hearing loss and imbalance problems, >25% of the patients showed additional
      symptoms, including episodes of vertigo, tinnitus, aural fullness and hearing
      loss. Clinically, these symptoms are consistent with the criteria for Meniere's
      disease. The importance of genetic factors in Meniere's disease has been
      suggested on many occasions, but this study is the first report of a mutation in 
      a gene leading to the symptoms of Meniere's disease in a significant portion of
      the carriers. The COCH gene may be one of the genetic factors contributing to
      Meniere's disease and the possibility of a COCH mutation should be considered in 
      patients with Meniere's disease symptoms.
FAU - Fransen, E
AU  - Fransen E
AD  - Department of Medical Genetics, University of Antwerp (UIA), Universiteitsplein
      1, B-2610 Antwerp, Belgium,
FAU - Verstreken, M
AU  - Verstreken M
FAU - Verhagen, W I
AU  - Verhagen WI
FAU - Wuyts, F L
AU  - Wuyts FL
FAU - Huygen, P L
AU  - Huygen PL
FAU - D'Haese, P
AU  - D'Haese P
FAU - Robertson, N G
AU  - Robertson NG
FAU - Morton, C C
AU  - Morton CC
FAU - McGuirt, W T
AU  - McGuirt WT
FAU - Smith, R J
AU  - Smith RJ
FAU - Declau, F
AU  - Declau F
FAU - Van de Heyning, P H
AU  - Van de Heyning PH
FAU - Van Camp, G
AU  - Van Camp G
LA  - eng
GR  - DC03402/DC/NIDCD NIH HHS/United States
GR  - DC03544/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (COCH protein, human)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Chromosomes, Human, Pair 14/genetics
MH  - DNA/chemistry/genetics
MH  - DNA Mutational Analysis
MH  - Extracellular Matrix Proteins
MH  - Family Health
MH  - Female
MH  - Genetic Linkage
MH  - Hearing Loss, Sensorineural/genetics
MH  - Humans
MH  - Lod Score
MH  - Male
MH  - Meniere Disease/epidemiology/*genetics/pathology
MH  - Microsatellite Repeats
MH  - Mutation
MH  - Pedigree
MH  - Prevalence
MH  - Proteins/*genetics
EDAT- 1999/07/13 00:00
MHDA- 1999/07/13 00:01
CRDT- 1999/07/13 00:00
PHST- 1999/07/13 00:00 [pubmed]
PHST- 1999/07/13 00:01 [medline]
PHST- 1999/07/13 00:00 [entrez]
AID - ddc164 [pii]
AID - 10.1093/hmg/8.8.1425 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Aug;8(8):1425-9. doi: 10.1093/hmg/8.8.1425.