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Science 20 March 1998:
Vol. 279. no. 5358, pp. 1950 - 1954
DOI: 10.1126/science.279.5358.1950
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Reports

Mutation in Transcription Factor POU4F3 Associated with Inherited Progressive Hearing Loss in Humans

Oz Vahava, * Robert Morell, * Eric D. Lynch, * Sigal Weiss, Marjory E. Kagan, Nadav Ahituv, Jan E. Morrow, Ming K. Lee, Anne B. Skvorak, Cynthia C. Morton, Anat Blumenfeld, Moshe Frydman, Thomas B. Friedman, Mary-Claire King, Karen B. Avraham dagger

The molecular basis for autosomal dominant progressive nonsyndromic hearing loss in an Israeli Jewish family, Family H, has been determined. Linkage analysis placed this deafness locus, DFNA15, on chromosome 5q31. The human homolog of mouse Pou4f3, a member of the POU-domain family of transcription factors whose targeted inactivation causes profound deafness in mice, was physically mapped to the 25-centimorgan DFNA15-linked region. An 8-base pair deletion in the POU homeodomain of human POU4F3 was identified in Family H. A truncated protein presumably impairs high-affinity binding of this transcription factor in a dominant negative fashion, leading to progressive hearing loss.

O. Vahava, S. Weiss, M. E. Kagan, N. Ahituv, K. B. Avraham, Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
R. Morell and T. B. Friedman, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health, Bethesda, MD 20850, USA.
E. D. Lynch, J. E. Morrow, M. K. Lee, M.-C. King, Departments of Medicine and Genetics, University of Washington, Seattle, WA 98195, USA.
A. B. Skvorak and C. C. Morton, Department of Pathology and Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
A. Blumenfeld, Unit for Development of Molecular Biology and Genetic Engineering, Hadassah University Hospital, Mt. Scopus, Jerusalem 91240, Israel.
M. Frydman, Genetics Institute, Haim Sheba Medical Center, Tel Hashomer 52621, Israel, and Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
*   These authors contributed equally to this report.

dagger    To whom correspondence should be addressed. E-mail: karena{at}post.tau.ac.il

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