ABSTRACT
Congenital hearing loss is one of the most frequent inherited human pathologies, occurring in 1-2 out of 1000 newborns. X-linked hearing loss occurs in 1-5% of all congenital hearing impairments. The proband (a man) and his affected brother have profound prelingual non-syndromic neurosensory hearing loss. Their parents are healthy. The aim of the study was to determine the cause of hearing loss in a given family and to assess the population frequency of the revealed pathogenic genetic variant. NGS analysis identified a pathogenic variant c.907C>T (p.Pro303Ser) in the POU3F4 gene mapped to the Xq21.1 locus. This is the second case of X-linked hearing loss (DFNX2, OMIM 304400) in Europe, caused by the c.907C>T variant in the POU3F4 gene. DFNX2-hearing loss is manifested with abnormalities of the inner ear, predisposing to the "gusher effect" - otoliquorrhea during stapedoplasty. The brother was diagnosed with a c.907C>T variant in the POU3F4 gene in the hemizygous state while in their mother - in the heterozygous state. Their father had no variant c.907C>T. Molecular genetic analysis showed that the genetic variant c.907C>T was not detected in the control sample of healthy female from the Nogai population, which suggests its low frequency in the population.
