MUTATION IN TRANSCRIPTION FACTOR POU4F3 ASSOCIATED WITH INHERITED PROGRESSIVE HEARING-LOSS IN HUMANS

The molecular basis for autosomal dominant progressive nonsyndromic he aring loss in an Israeli Jewish family, Family H, has been determined. Linkage analysis placed this deafness locus, DFNA15, on chromosome 5q 31, The human homolog of mouse Pou4f3, a member of the POU-domain fami ly of transcription factors whose targeted inactivation causes profoun d deafness in mice, was physically mapped to the 25-centimorgan DFNA15 -linked region. An 8-base pair deletion in the POU homeodomain of huma n POU4F3 was identified in Family H. A truncated protein presumably im pairs high-affinity binding of this transcription factor in a dominant negative fashion, leading to progressive hearing loss.