Genetic map localization of DFNA34 and DFNA36, two autosomal dominant nonsyndromic deafness loci. K. Kurima¹, Y. Szymko², S. Rudy², R.J. Morell¹, T.B. Friedman¹, A.J. Griffith^1,2. 1) Laboratory of Molecular Genetics; 2) Neuro-otology Branch, NIDCD, NIH, Rockville, MD.
   Hereditary deafness is genetically heterogeneous, and it is estimated that hundreds of genes may cause nonsyndromic sensorineural deafness. The identification of these genes associated with hearing loss continues to reveal the molecular mechanisms underlying the evolution, development, structure, and physiology of the auditory system, as well as the pathogenesis of hereditary hearing loss. We have ascertained two families, LMG113 and LMG128, segregating autosomal dominant, progressive, postlingual, nonsyndromic sensorineural hearing loss. The onset of the auditory phenotype in LMG128 occurs during the first decade of life and rapidly progresses to profound deafness by early adulthood, whereas LMG113 segregates a less severe phenotype that becomes clinically detectable during the third or fourth decade of life and progresses at a much slower rate. Genotype analysis excluded linkage to known dominant deafness loci in both families. A genome-wide linkage scan with STR markers revealed linkage of the deafness phenotype in LMG113 to a 14-cM region between markers D1S102 and D1S3739 on chromosome 1q44 (max. LOD = 3.33 at q = 0 for D1S2836). The obligate interval of this locus, designated DFNA34, overlaps that of the locus for Muckle-Wells syndrome (MWS), a dominant disorder characterized by periodic systemic inflammatory episodes and progressive sensorineural hearing loss. The overlap in phenotype and genetic locations suggest that DFNA34 and MWS may be allelic. Sensorineural hearing loss in LMG128 was linked to a 12-cM region between markers D9S1118 and D9S175 on chromosome 9q13-q21 (max. LOD = 5.51 at q = 0 for D9S1876). This locus was designated DFNA36, and its critical interval overlaps those for the nonsyndromic recessive deafness loci DFNB7/11, suggesting that these loci may represent allelic disorders. Linkage analysis of additional families such as LMG113 and LMG128 will contribute to the identification of the genes for deafness and will give insight into the pathophysiology and normal biological functions of these genes in the auditory system.