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. Study Design: This was a genetic study of a single Japanese family with DFNS. 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. Conclusion: Microdeletions at a previously undescribed location account for some clinically important POU3F4 mutations.