LINKAGE OF AUTOSOMAL-DOMINANT HEARING-LOSS TO THE SHORT ARM OF CHROMOSOME-1 IN 2 FAMILIES

Background. At least half of the cases of profound deafness of early o nset are caused by genetic factors, but few of the genetic defects hav e been identified. This is particularly true of the most common heredi tary forms of deafness, which occur in the absence of any associated s yndrome. Methods. We studied a large Indonesian family in which hearin g loss was inherited in an autosomal dominant pattern. The hearing los s first affects the high frequencies during the teens or 20s and becom es profound within 10 years. To locate the responsible gene, we perfor med genetic-linkage analysis, using microsatellite markers distributed over the entire genome. We then performed linkage analyses in an Amer ican family and a Dutch family with similar patterns of hereditary hea ring loss. Results. In the extended Indonesian family, a gene linked t o deafness mapped to chromosome Ip, with a multipoint rod score of mor e than 7. In the American family, deafness was linked to the same locu s on chromosome 1p, with a multipoint rod score of more than 5. In the Dutch family, however, this locus was ruled out. The flanking markers D1S255 and D1S211 defined a region of 6 cM on chromosome 1p that is l ikely to contain the gene associated with deafness in the first two fa milies. Conclusions. In some families with early-onset autosomal domin ant hearing loss, the responsible gene is on chromosome 1p.