Association Between X-Linked Mixed Deafness and Mutations in the POU Domain Gene <i>POU3F4</i>

TLDR

DFN3, the most common X‑linked deafness, is caused by a gene located in a 500‑kb region on Xq21. The study reports that the transcription factor gene POU3F4, encoding a POU domain protein, maps to this same interval. Mutations truncating or altering POU3F4 were found in five DFN3 patients but not in 50 controls, confirming POU3F4 as the molecular cause of DFN3.

Abstract

Deafness with fixation of the stapes (DFN3) is the most frequent X-linked form of hearing impairment. The underlying gene has been localized to a 500-kilobase segment of the Xq21 band. Here, it is reported that a candidate gene for this disorder, Brain 4 ( POU3F4 ), which encodes a transcription factor with a POU domain, maps to the same interval. In five unrelated patients with DFN3 but not in 50 normal controls, small mutations were found that result in truncation of the predicted protein or in nonconservative amino acid substitutions. These findings indicate that POU3F4 mutations are a molecular cause of DFN3.