title: Identification of a novel mutation in POU3F4 for prenatal diagnosis in a Chinese family with X-linked nonsyndromic hearing loss.
abstract: We present the clinical and genetic findings for a Chinese family with X-linked non-syndromic hearing loss in which the affected males showed congenital profound sensorineural hearing impairment. In two affected brothers, the computer tomography of temporal bone showed bilateral dilation of the internal auditory canal with fistulous communication between the lateral canal and the basal cochlear turn, which is consistent with the typical DFNX2 phenotype. A missense mutation (c.647G→A) in the POU3F4 gene caused a substitution from glycine to glutamic acid at position 216 (p.G216E), and this mutation was found to consistently cosegregate with the deafness phenotype in the family. The mutation resulted in the loss of function of the POU3F4 by decreasing the affinity between the protein and DNA, as shown in silico by the structural analysis. Prenatal diagnosis of pregnant proband of this family revealed the c.647G→A mutation in DNA extracted from the amniotic fluid surrounding the fetus. The appropriate use of genetic testing and prenatal diagnosis plays a key role in reducing the recurrence of genetic defects in high-risk families.
authors.affiliation: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.forename: Yanping
authors.initials: Y
authors.lastname: Lu
authors.forename: Yu
authors.initials: Y
authors.lastname: Lu
authors.forename: Aiting
authors.initials: A
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.forename: Dongyang
authors.initials: D
authors.lastname: Kang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
authors.forename: Dongyi
authors.initials: D
authors.lastname: Han
authors.forename: Huijun
authors.initials: H
authors.lastname: Yuan
mesh_terms: D044466:Asian People / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D007758:Ear, Inner / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D018698:Glutamic Acid / Q000235:genetics; D005998:Glycine / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D020125:Mutation, Missense; D050809:POU Domain Factors / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D013701:Temporal Bone / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed
chemical_list: D050809:POU Domain Factors; C091774:POU3F4 protein, human; D018698:Glutamic Acid; D004247:DNA; D005998:Glycine