Hearing loss has many known genetic and environmental causes and affects at least 30 percent of the population at some time in their lives. The incidence of profound deafness at birth is about 0.8 per 1000. However, newborn hearing screening programs have shown that another 1-2 infants per 1000 have a lesser but clinically significant loss of 30dB or more in at least one ear. A remarkable feature of the genetic epidemiology of deafness was the recent discovery that, although there are many genes that can cause deafness, in many countries recessive mutations at a single locus, DFNB1, involving the GJB2 gene, which encodes the gap junction protein connexin 26, account for 30-40 percent of all cases. In 1898, E.A. Fay, a professor at Gallaudet University, published his monumental treatise """"""""Marriages Among the Deaf in America"""""""" in which he documented hearing loss in the families of nearly 5000 marriages of the deaf in America during the 19th century. This powerful data set has been repeatedly re-analyzed during the past 100 years, and remains unique because the families were ascertained by complete selection through deaf parents. Our goal is to extend Fay's study by combining family histories obtained from Gallaudet alumni with more contemporary clinical and molecular phenotyping for GJB2 and other genes. We propose to systematically ascertain Gallaudet alumni and obtain questionnaire data as well as blood samples, which will allow us to characterize the frequency, clinical phenotype and spectrum of mutations at specific gene loci for syndromic and non- syndromic deafness. The resulting data will provide key observations on the secular trends in demographic and epidemiologic variables. We also will obtain contemporary estimates of the frequency of non-complementary (producing only deaf children) matings between deaf partners. The genotypic characterization of marriages among the deaf represents a novel strategy to search for interactions between rare non-allelic genes. This is a research opportunity, which is rapidly diminishing, as educational mainstreaming and the use of cochlear implants continue to erode the deaf culture, making matings between deaf partners less likely in the future. ? ?
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