DFNA27, a new locus for autosomal dominant hearing impairment on chromosome 4. R.A. Fridell¹, E.A. Boger¹, T. San Agustin², M.J. Brownstein³, T.B. Friedman¹, R.J. Morell¹. 1) Lab. Molecular Genetics, NIDCD, NIH, Rockville, MD; 2) NIDRR, DOEd, Washington D.C; 3) Lab. of Genetics, NIMH, NHGRI, NIH, Bethesda, MD.

   Nonsyndromic hereditary hearing impairment is an extremely heterogeneous disorder. The continued identification of genes associated with hearing loss provides an effective means of uncovering essential components of the auditory system and promises an increased understanding of the molecular basis for sound transduction. We have ascertained a family segregating autosomal dominant nonsyndromic sensorineural hearing loss. In eleven affected individuals in this family, age of onset for the hearing loss was variable, ranging from pre-teens to late twenties. Affected individuals under the age of 40 years exhibit moderate to profound hearing loss (~30-90 dB). In older affected individuals, hearing loss is profound (> 90 dB). To map the locus responsible for hearing loss in this family, we first excluded known deafness loci and then performed a genome-wide scan with STR markers from the Weber 8 screening panel. Strong evidence for linkage was found to an approximately 15 cM region between markers D4S428 and D4S392 (maximum LOD= 4.76 at q = 0 for D4S3248). This region does not contain any other known nonsyndromic deafness genes and the new locus has been designated DFNA27. Progress in refining the DFNA27 genetic interval and identifying candidate genes will be reported.