Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans.
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.
Vahava
O
O
Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Morell
R
R
Lynch
E D
ED
Weiss
S
S
Kagan
M E
ME
Ahituv
N
N
Morrow
J E
JE
Lee
M K
MK
Skvorak
A B
AB
Morton
C C
CC
Blumenfeld
A
A
Frydman
M
M
Friedman
T B
TB
King
M C
MC
Avraham
K B
KB
D000328:Adult; D000818:Animals; D002454:Cell Differentiation; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D008040:Genetic Linkage; D006198:Hair Cells, Auditory / Q000166:cytology / Q000502:physiology; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D017384:Sequence Deletion; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D018398:Homeodomain Proteins; C111223:POU4F3 protein, human; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors