A novel locus for autosomal dominant non-syndromic deafness (DFNA41) maps to chromosome 12q24-qter. X.Z. Liu^1,2, S.H. Blanton^1,3, C.Y. Liang², M.W. Cai², A. Pandya¹, B. Landa¹, S. Mummalanni¹, K.S. Li², L.L. Du², X.N. Qin², Y.F. Liu², W.E. Nance¹. 1) Dept Human Genetics, VCU, Medical Col Virginia, Richmond, VA; 2) Dept Otolaryngology, West China University of Medical Sciences, Chengdu, China; 3) Dept Pediatrics, University of Virginia, Charlottesville, Virginia.
   Hearing impairment is the most common sensory disorder in humans, and genetic factors are a major cause. Approximately 80% of hereditary hearing loss is non-syndromic without associated abnormalities. It is estimated that 15-25% of these cases exhibit an autosomal dominant pattern of transmission. At least 40 autosomal dominant loci have been mapped todate, and of these, 13 have been cloned. We have mapped a novel locus for autosomal dominant non-syndromic hearing loss, DFNA41, to chromosome 12q24-qter in a large multigenerational Chinese family with progressive hearing impairment. Most affected individuals noticed hearing impairment after their teens with subsequent gradual progression from moderate to profound loss. All affected individuals had bilateral sensorineural hearing loss involving all frequencies. There were no obvious vestibular dysfunction and other associated abnormalities. Following a genome wide scan performed by CIDR, a maximum multipoint lod score of 8.97 was obtained at marker D12S343. While multipoint analysis places the DFNA41 locus distal to D12S1609, there was no recombination with other more distal markers to permit identification of a distal flanking marker. Another deafness locus, DFNA25, has been mapped to 12q21-q24. We excluded linkage of the markers surrounding this locus to our family. The DFNA41 interval begins approximately 35 cM distal to DFNA25. Numerous genes are known to map to the region, and among the positional candidate genes, those functionally related to hearing or expressed in the inner ear are being screened for deafness-causing mutations. This work was supported by NIDCD grants DC04530, DC02530, and DC 04282.