EVIDENCE FOR DIGENIC INHERITANCE OF NONSYNDROMIC HEREDITARY HEARING-LOSS IN A SWEDISH FAMILY

We investigated a Swedish family with nonsyndromic progressive bilater al sensorineural hearing loss. Thirteen candidate loci for autosomal d ominant nonsyndromic hearing loss were tested for linkage in this fami ly. We found significant LOD scores (>3) for markers at candidate locu s DFNA12 (11q22-q24) and suggestive LOD scores (>2) for markers at loc us DFNA2 (1p32). Our results for markers on chromosome 11 narrowed dow n the candidate region for the DFNA12 locus. A detailed analysis of th e phenotypes and haplotypes shared by the affected individuals support ed the notion that two genes segregated together with hearing impairme nt in the family. Severely affected family members had haplotypes link ed to the disease allele on both chromosomes 1 and 11, whereas individ uals with milder hearing loss had haplotypes linked to the disease all ele on either chromosome 1 or chromosome 11. These observations sugges t an additive effect of two genes, each gene resulting in a mild and s ometimes undiagnosed phenotype, but both together resulting in a more severe phenotype.