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 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Animals
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Cell Differentiation
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Chromosome Mapping
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Chromosomes, Human, Pair 5 / genetics
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Deafness / genetics*
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Female
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Gene Expression
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Genetic Linkage
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Hair Cells, Auditory / cytology
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Hair Cells, Auditory / physiology
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Hearing Loss, Sensorineural / genetics*
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism
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Humans
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Israel
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Jews / genetics
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Male
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Mice
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Middle Aged
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Molecular Sequence Data
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Pedigree
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Polymerase Chain Reaction
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Protein Structure, Secondary
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Sequence Deletion
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Transcription Factor Brn-3C
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcription Factors / physiology
Substances
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Homeodomain Proteins
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POU4F3 protein, human
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Transcription Factor Brn-3C
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Transcription Factors
Associated data
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GENBANK/AF043452
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GENBANK/S69352
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GENBANK/U10060
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GENBANK/U10061