A GENE FOR AUTOSOMAL-DOMINANT NONSYNDROMIC HEREDITARY HEARING IMPAIRMENT MAPS TO 4P16.3

Mapping genes for nonsyndromic hereditary hearing impairment may lead to identification of genes that are essential for the development and preservation of hearing. We studied a family with autosomal dominant, progressive, low frequency sensorineural hearing loss. Linkage analysi s employing microsatellite polymorphic markers revealed a fully linked marker (D4S126) at 4p16.3, a gene-rich region containing IT15, the ge ne for Huntington's disease (HD). For D4S126, the logarithm-of-odds (l ed) score was 3.64 at theta = 0, and the overall maximum lod score was 5.05 at theta = 0.05 for D4S412. Analysis of recombinant individuals maps the disease gene to a 1.7 million base pair (Mb) region between D 4S412 and D4S432, Genes for two types of mutant mice with abnormal coc hleovestibular function, tilted (tit) and Bronx waltzer (by), have bee n mapped to the syntenic region of human 4p16.3 on mouse chromosome 5. Further studies with the goals of cloning a gene for autosomal nonsyn dromic hearing impairment and identifying the murine homologue may exp lain the role of this gene in the development and function of the coch lea.