REFINED MAPPING OF A GENE FOR AUTOSOMAL-DOMINANT PROGRESSIVE SENSORINEURAL HEARING-LOSS (DFNA5) TO A 2-CM REGION, AND EXCLUSION OF A CANDIDATE GENE THAT IS EXPRESSED IN THE COCHLEA

A gene for an autosomal dominant form of progressive sensorineural hea ring loss (DFNA5) was previously assigned by us to a 15-cM region on c hromosome 7p15. In this study, the DFNA5 candidate region was refined to less than 2 cM, and completely cloned in a YAC contig. The HOXA1 ge ne located in 7p15 was considered to be a good candidate gene for DFNA 5 as it harbours mutations leading to developmental defects of the inn er ear in mice. However, the refinement of the candidate region of DFN A5 excludes the HOXA1 gene as a candidate for DFNA5. We cloned a novel candidate gene (CG1, candidate gene 1), which is expressed in human f etal cochlea, from the DFNA5 candidate region. The complete cDNA seque nce of CG1, encoding a 423 amino acid protein of unknown function, was determined. Mutation analysis of the CG1 gene in DFNA5 patients, howe ver, could not reveal a disease-causing mutation.