POU3F4 and Mixed Deafness with Temporal Bone Defect (DFN3)

Abstract

Abstract X-linked deafness type 3 (DFN3; McKusick 304400) is characterized by temporal bone abnormalities, stapes fi xation, and, in most cases, a mixed type of deafness. During stapes surgery, a flow of cerebrospinal fluid (“gusher”) is encountered. High-resolution computer assisted tomography has revealed a bulbous dilatation of the lateral portion of the internal auditory canal (IAC) with incomplete separation from the cochlea, and widening of the fi rst part of the facial nerve canal. DFN3 is the most frequent form of X-linked deafness and is caused by muta-tions in the POU3F4 gene, or by deletions overlapping an 8 kb DNA segment located 900 kb proximal to the POU3F4 gene. POU3F4 and its mouse orthologue Pou3f4, are expressed in the developing inner ear, neural tube, pancreas, kidney, and muscle. The gene plays crucial roles in the patterning of the mesenchymal compartment of the inner ear. A mouse mutant that arose in a radiation mutagenesis experiment, sex-linked fidget (slf ), carries an inversion that abolishes Pou3f4 gene expression in the embryonic inner ear, but not in the neural tube, corroborating the existence of an inner-ear-specifi c regulatory DNA element located far upstream of the mouse and human POU3F4 genes.