A new locus for autosomal dominant hearing loss DFNA28 mapped to chomosome 8q22. D.W. Anderson¹, A.J. Griffith¹, S. Rudy¹, T. San Agustin², T.B. Friedman¹, R.J. Morell¹. 1) Laboratory of Molecular Genetics, NIDCD, NIH, Rockville, MD; 2) NIDRR, U.S. Dept. of Education, Washington, DC.

   We have ascertained a large American family with an autosomal dominant form of nonsyndromic sensorineural hearing loss. The hearing loss is postlingual, with an onset as early as seven years of age, and gradual progression to moderate to severe levels by the fifth decade. The audiometric pattern is variable, with predominant impairment of high frequencies in some affected individuals and middle frequencies in others. Speech discrimination scores are normal, indicating that the loss is cochlear in origin.
   Twenty-four individuals from four generations, including 9 affected individuals, were initially screened with STR markers linked to the reported DFNA and DFNB loci. These loci were all eliminated from consideration on the basis of two point linkage analysis. A genome wide scan using the Weber 8 panels was performed. Linkage to marker GAAT1A4 , at 8q22, was detected with a LOD (z) = 4.86 at q = 0. Haplotype analysis using markers flanking GAAT1A4 defined a 4 cM critical region between markers D8S546 and D8S545. This region excludes two loci for syndromic deafness: Branchio-Oto-Renal syndrome (BOR) and Hereditary Motor Sensory Neuropathy-Lom (HMSNL). There are no nonsyndromic deafness loci mapped to chromosome 8q22. Therefore, this family represents a new deafness locus, DFNA 28.