High prevalence of symptoms of Meniere's disease in three families with a mutation in the COCH gene

We report the genetic analysis of one large Belgian and two small Dutch fam ilies with autosomal dominant nonsyndromic progressive sensorineural hearin g loss associated with vestibular dysfunction, Linkage studies in the Belgi an family mapped the disease to the DFNA9 locus on chromosome 14, Mutation analysis of the COCH gene, which is responsible for DFNA9, revealed a misse nse 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 wa s found in the Belgian family, we discovered that the same missense mutatio n was also present in two Dutch families with similar cochleo-vestibular sy mptoms. 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 gene tic 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 sympt oms 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 a nd the possibility of a COCH mutation should be considered in patients with Meniere's disease symptoms.