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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

283 Scopus citations

Abstract

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 Pou413, 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.

Original languageEnglish
Pages (from-to)1950-1954
Number of pages5
JournalScience
Volume279
Issue number5358
DOIs
StatePublished - 20 Mar 1998

Funding

FundersFunder number
National Institute on Deafness and Other Communication DisordersR01DC001076

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