THE CONTRIBUTION OF THE DFNB1 LOCUS TO NEUROSENSORY DEAFNESS IN A CAUCASIAN POPULATION

Classical studies have demonstrated genetic heterogeneity for nonsyndr omic autosomal recessive congenital neurosensory deafness, with at lea st six loci postulated. Linkage analysis in two consanguineous Tunisia n kindreds has demonstrated that one such deafness locus, DFNB1, maps near chromosome 13 markers D13S175, D13S143, and D13S115. We tested th ese markers for cosegregation with deafness in 18 New Zealand and 1 Au stralian nonconsanguineous kindreds, each of which included at least t wo siblings with nonsyndromic presumed congenital sensorineural deafne ss and that had a pedigree structure consistent with autosomal recessi ve inheritance. When all families were combined, a peak two-point lod score of 2.547 (theta = .1) was obtained for D13S175, 0.780 (theta = . 2) for D13S143, and 0.664 (theta = .3) for D13S115. While there was no statistically significant evidence for heterogeneity at any of the th ree loci tested, nine families showed cosegregation of marker haplotyp es with deafness. These observations suggest that the DFNB1 locus may make an important contribution to autosomal recessive neurosensory dea fness in a Caucasian population. In the nine cosegregating families, p henotypic variation was observed both within sibships (in four familie s), which indicates that variable expressivity characterizes some geno types at the DFNB1 locus, and between generations (in two families), w hich suggests allelic heterogeneity.