PDFlib PLOP: PDF Linearization, Optimization, Protection Page inserted by evaluation version www.pdflib.com – sales@pdflib.com zyx zyxw Ascertainment of Families with Hereditary Deafness for Linkage Studies Waardenburg and Usher Syndromes zyxwv C. STEVENS: K. ARNOS,C J. BODURTHA: L. WRIGHT: B. RAWLINGS; M. MARAZITA: W. NANCE,a AND S. DIEHLarb aDepartment of Human Genetics bDepartment of Psychiatiy Medical College of Hrginia Richmond, Hw’nia 23298 CGallaudetResearch Institute and Genetic Services Center Gallaudet University Washington,D. C. 20002 We have made use of the Annual Survey of Hearing Impaired Children and Youth to obtain valuable information regarding the hereditary basis of deafness. This survey is administered by the Center for Assessment and Demographic Studies at Gallaudet University and is sent to over 50,000 students each year. Our research group provided a one-page supplementary questionnaire that was included with the standard survey forms that were distributed in the fall of 1988. This questionnaire was mailed to over 28,000 students who had responded to previous survey questions regarding the cause of hearing loss as either “hereditary” or “unknown.” Our supplementary questionnaire included a number of questions addressing the familial basis of deafness, and will provide a wealth of information regarding the overall genetic basis of hereditary deafness. The 1988 questionnaire replicates a previous genetics questionnaire distributed in 1970,’thus allowing for an assessment of the possible occurrence of any significant changes in the hereditary versus environmental basis of deafness. It also included questions regarding the possible occurrence of Waardenburg and Usher syndromes. These are shown in TABLE 1. A total of over 8700 individuals responded to our supplementary questionnaire, of whom 900 responded positively to the query regarding Usher syndrome, and 1460 to the query regarding Waardenburg syndrome. These individuals were sent follow-up consent forms asking their permission to be contacted by telephone to assess the etiology of their particular cases of deafness. We have been focusing our recruitment efforts on Waardenburg syndrome at this time. To date, 552 individuals who responded positively to the Waardenburg syndrome question have returned these consent forms, of whom 175 have been interviewed by telephone. Based on these interviews, we estimate that we have identified 32 probable cases of Waardenburg syndrome (confirmed either by photograph or diagnosis of a clinical geneticist). These include 3 probable new mutations and 27 extended pedigrees (a total of about 343 individuals). In addition, we have identified 21 other families with possible Waardenburg syndrome (diagnostic confirmation not yet available). We have already recruited 5 families into participation in our linkage study, and have obtained 30 blood samples for establishing immortalized zyxwvuts 293 294 zyxwvutsrq zyxwvutsrqpon zyxwv zyx ANNALS NEW YORK ACADEMY OF SCIENCES Supplementary Questions Added to the 1988Annual Survey of Hearing Impaired Children and Youth TABLE 1. zyx 1. Does this student or a relative of this student have any one or more of the following: different color eyes, a white forelock, grey hair before age 30, or Waardenburg syndrome? Yes Do Not Know - No 2. Does this student or a relative of tz student have any one or more of the following: progressive loss of vision, night blindness, retinitis pigmentosa, or Usher syndrome? - Do Not Know - Yes - No zyxwvu lymphoblastoid cell lines and for genotyping of DNA polymorphisms for linkage analyses aimed at mapping the gene(s) underlying this disorder. These include 1 new mutation family and 4 extended pedigrees. Our preliminary data obtained thus far provide reason for hope that this approach may be successful for identifying a large number of families affected by hereditary deafness, a resource of great potential benefit for research into the underlying etiology. zyxwvut REFERENCES & W. E. NANCE.1977. Genetic analysis of childhood 1. ROSE, S. P., P. M. CONNEALLY deafness. In Childhood Deafness. F. H. Bess, Ed.: 9-35. Grune & Stratton. New York, N.Y.