A new locus for dominant progressive hearing loss DFNA37 mapped to chromosome 1p21. Z. Talebizadeh¹, J.B. Kenyon², J.W. Askew¹, S.D. Smith². 1) Genetics, Boys Town Natl Res Hosp, Omaha, NE; 2) University of Nebraska Medical Center, Omaha, NE.
   In this study we have shown linkage of dominant progressive hearing loss in a 4-generation American family (family 513) to chromosome 1p21. Linkage analysis with markers from ABI Prism panels produced a lod score of 8.29 for marker D1S495 at q=0.0. Hearing loss appears to be completely penetrant, and affected individuals experience an early-onset high frequency hearing loss which progressed with age to include middle and lower frequencies. The craniofacial features of affected family members are entirely normal, and there is no history of ocular abnormalities nor cleft palate in the family. Affected individuals do appear clinically to have some widening of the epiphyses of the long bones, however X-rays from the proband ruled out any abnormalities in his knees. The COL11A1 gene is one of the genes in the linked region. Both linkage analysis and involvement of the COL11A1 gene in Marshall and Stickler syndromes suggested this gene as a strong candidate for mutation analysis in family 513. The entire coding region of COL11A1 was screened and this collagen gene was strongly excluded for this family. A shaw-related potassium channel gene, KCNC4, was also considered as a candidate gene. No mutation was observed in the pore region of KCNC4, in association with hearing loss in family 513. The linked region is being further searched for another candidate gene. To date, there has not been any report of linkage of non-syndromic hearing loss to chromosome 1p21. This new locus is designated as DFNA37. Since the only gene involved in hearing loss in this chromosomal band is COL11A1, which was excluded in family 513, identification of the deafness gene in this family will add a new gene involved in auditory function.