A new mutation in the POU3F4 gene in a Japanese family with X-linked mixed deafness (DFN3).
OBJECTIVE
The molecular defect in patients with X-linked mixed deafness showing a perilymphatic gusher at stapedectomy (DFN3) has been attributed to mutations in the POU3F4 gene. This study aimed to clarify an allelic variant of this gene.


METHODS
This was a genetic study of a single Japanese family with DFN3.


METHODS
Products of a polymerase chain reaction (PCR) were subjected to single-strand conformation polymorphism (SSCP) analysis. Direct sequencing of PCR products from patients and carriers showing SSCP variants was performed using the fluorescent dideoxy termination method and a sequencer.


RESULTS
Sequencing of the PCR product revealed a 6-base deletion (TTCAAA) at nucleotides 601 to 606, resulting in a two-amino-acid deletion in the POU3F4 protein, (phenylalanine and lysine at amino acid residues 201 and 202). The deletion was adjacent to the site of a nonsense mutation previously described.


CONCLUSIONS
Microdeletions at a previously undescribed location account for some clinically important POU3F4 mutations.
Department of Otorhinolaryngology, Jichi Medical School, Tochigi, Japan.
H
H
Hagiwara
Y
Y
Tamagawa
K
K
Kitamura
K
K
Kodera
D044466:Asian People / Q000235:genetics; D001301:Audiometry, Pure-Tone; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D050809:POU Domain Factors; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014157:Transcription Factors / Q000235:genetics*; D014960:X Chromosome
D050809:POU Domain Factors; C091774:POU3F4 protein, human; D014157:Transcription Factors