Preferred Minimum: 8 mL whole blood Absolute Minimum: 4 mL whole blood

DFN3 Deafness at the DFN3 locus can be conductive (due to impaired stapes mobility) and/or mixed with a superimposed, often progressive, sensorineural component. Stapedectomy to correct the conductive component is contraindicated because of the possibility of iatrogenic profound hearing loss secondary to a stapes gusher. A stapes gusher occurs because the internal auditory canal is abnormally dilated. The wide communication between the internal auditory canal and inner ear can often be visualized by computerized tomography. The gene, POU3F4, was found to be responsible for this form of X-linked hearing loss by De Kok and colleagues. POU3F4 The single exon of POU3F4 encodes a transcription factor with a 75 amino acid POU domain and a 63 amino acid homeobox domain. In animal studies, Minowa and colleagues showed Brn4 (Pou3f4) deficient mice have profound deafness and inner ear abnormalities. In humans with DFN3, mutations have been found in either of the two binding domains, as well as upstream of POU3F4. In the presence of these large upsteam deletions, the coding sequence of POU3F4 can be entirely normal. Sensitivity is greater than 99% for coding sequence analysis of POU3F4. The sensitivity of the deletion screen is unknown.