Prelingual deafness is etiologically heterogeneous with many known genetic and environmental causes. Its incidence at birth or during early childhood in this country is about 0.8 per 1,000. Previous studies have shown that mutations in nuclear or mitochondrial genes account for about half of all cases of profound deafness. In about 80-90% of these cases, genetic deafness occurs as an isolated abnormality, with recessive transmission being the most common pattern of inheritance. It is estimated that genes at least 36-103 independent loci are capable of producing deafness. The chromosomal locations of 22 genes for non-syndromic deafness have already been established, but the relative frequency of mutations at these loci represents an important gap in existing knowledge. The goal of this research is to determine the frequencies of mutations at these loci and to map additional deafness loci. Over the five years of the proposed study, the investigators will (1) ascertain large multigenerational pedigrees and smaller consanguineous pedigrees through the resources of Gallaudet University in Virginia and the School for the Deaf in Ulaanbaatar, Mongolia; (2) test for linkage in these families to known deafness genes and seek to identify mutations in those families showing linkage to these genes; (3) carry out a 10 cM genome screen on 8-13 large multigenerational pedigrees with a total of about 235 individuals and on 340 consanguineous families, about half of which will be multiplex; (4) follow up initial suggestions of linkage in these families in an effort to confirm and fine map the responsible genes; and (5) begin to identify the genes primarily by means of the positional candidate strategy. A total of about 50,000 genotypings will be performed each year. In addition, blood spots from all available students at the School for the Deaf in Ulaanbaatar will be screened for the mitochondrial mutation that is associated with sensitivity to streptomycin.
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