POU3F4 Gene Test for X-Linked Hearing Loss Details
Hearing loss caused by pathogenic variants in the POU3F4 gene accounts for approximately 40% of X-linked nonsyndromic hearing loss. Individuals, usually males, with variants in this gene have characteristic clinical and radiological features, in particular a perilymphatic flow (or "gusher") that can occur during stapes surgery. The hearing loss in these individuals can be mixed with the sensorineural component usually presenting in infancy and showing progression with age. The conductive hearing loss component, which may or may not be present, is due to fixation of the stapes. Importantly, if POU3F4 testing is positive, a stapes surgery is contraindicated due to the occurrence of a perilymphatic gusher, which can worsen the severity of the hearing loss. Vestibular problems and temporal bone abnormalities such as dilatation of the lateral end of the internal auditory meatus (IAM) and/or deficiency of bone between the basal turn of the cochlea and the IAM are also common. Female carriers of a POU3F4 variant may show a slight hearing loss with or without the perilymphatic gusher, most likely due to skewed X-inactivation. Children of a female with an identified pathogenic variant in POU3F4 will have a 50% risk of inheriting the same variant. Male offspring carrying the pathogenic variant will be affected. Females will be carriers or mildly affected. An affected male will pass along a pathogenic variant to all of his daughters, but none of his sons. De novo variants and somatic mosaicism have been reported (de Kok 1997 PMID: 9298820).
|POU3F4||Pou Domain, Class 3, Transcription Factor 4||300039||Xq21.1|
Sequencing of the POU3F4 gene is recommended for males with hearing loss and identification of stapes fixation and perilymphatic gusher. Testing for POU3F4 may be indicated in a family with an X-linked pattern of nonsyndromic hearing loss, a history of vestibular problems, or temporal bone abnormalities associated with POU3F4 related hearing loss; however, additional genes associated with X-linked hearing loss have been identified, and are present on the OtoGenome™ Test. The detection of a pathogenic variant in POU3F4 will allow one to determine whether or not a stapedectomy is contraindicated.
Females with mild features or those with affected male relatives should also consider testing to determine carrier status.
This test is performed by Sanger sequencing of the coding regions and splice sites of the POU3F4 gene. This test does not detect large deletions or variants in non-coding regions that could affect gene expression cases.
Analytical and Clinical Sensitivity
This test is greater than 99.9% accurate in detecting variants in the sequence analyzed.
Pathogenic variants in the POU3F4 gene may account for approximately 40% of X-linked nonsyndromic hearing loss.