LINKAGE ANALYSIS OF PROGRESSIVE HEARING-LOSS IN 5 EXTENDED FAMILIES MAPS THE DFNA1 GENE TO A 1.25-MB REGION ON CHROMOSOME 1P

Thus far, 13 genes for autosomal dominant hearing loss have been local ized to specific chromosomal regions, but none of the genes has been c loned. Only a single family has been linked to each of these loci, wit h the exception of DFNA2, DFNA2 was originally mapped in two extended families originating from Indonesia and the United States. In this stu dy we report linkage to DFNA2 in three additional large families with autosomal dominant hearing loss from Belgium and The Netherlands. Thes e five DFNA2 families show a similar progressive sensorineural hearing loss, starting in the high frequencies and also affecting the middle and low frequencies later in life. Combining the information from all linked families, the candidate region that is most likely to contain t he DFNA2 gene was reduced to a 1.25-Mb region between markers D1S432 a nd MYCL1. Different haplotypes segregating with the hearing loss were found in all five families, suggesting that different mutations are pr esent in the same gene, These results indicate that DFNA2 is most like ly an important gene for autosomal dominant hearing loss. (C) 1997 Aca demic Press.