Objective： Based on the clinical manifestations of a hearing loss patient, the POU3F4 gene was tested for diagnosis of etiology. Methods： A comprehensive physical examination was performed on the proband to exclude ...Objective： Based on the clinical manifestations of a hearing loss patient, the POU3F4 gene was tested for diagnosis of etiology. Methods： A comprehensive physical examination was performed on the proband to exclude abnormalities of other organs, and detailed audi- ological testing and temporal bone CT scan were also performed. Genomic DNA was extracted using the proband＇s peripheral blood leukocytes. Polymerase chain reactions （PCR） were performed in the coding sequence of the POU3F4 gene. Direct DNA sequencing was subsequently applied to screen the entire coding region of the POU3F4 gene. Results： The proband had severe sensorineural hearing loss. Temporal CT showed bilateral cochlear incomplete partition, vestibule dysplasia, internal auditory canal fundus expansion, and cochlear interlink with the internal auditory canal fundus. A novel mutation （c.530C 〉 A （p.S 177X）） in the POU3F4 gene was found in this patient, creating an new stop codon and was predicted to result in a truncated protein lacking normal POU3F4 transcription factor function. Conclusion： Through analysis of the POU3F4 gene and clinical manifestations in the patient, we conclude that a novel mutation may have resulted in a premature stop codon, contributing to the mutation of POU3F4 gene.展开更多
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 broth...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 substitu- tion 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.展开更多
基金supported by Chinese National Nature Science Foundation(81230020)grant from Minister of Science and Technology of China(2012BAI09B02)to P.D.+2 种基金Chinese National Nature Science Foundation(81371098)Beijing Natural Science Foundation(7132177)Beijing Nova programme(2009B34)to Y.Y.Y
文摘Objective： Based on the clinical manifestations of a hearing loss patient, the POU3F4 gene was tested for diagnosis of etiology. Methods： A comprehensive physical examination was performed on the proband to exclude abnormalities of other organs, and detailed audi- ological testing and temporal bone CT scan were also performed. Genomic DNA was extracted using the proband＇s peripheral blood leukocytes. Polymerase chain reactions （PCR） were performed in the coding sequence of the POU3F4 gene. Direct DNA sequencing was subsequently applied to screen the entire coding region of the POU3F4 gene. Results： The proband had severe sensorineural hearing loss. Temporal CT showed bilateral cochlear incomplete partition, vestibule dysplasia, internal auditory canal fundus expansion, and cochlear interlink with the internal auditory canal fundus. A novel mutation （c.530C 〉 A （p.S 177X）） in the POU3F4 gene was found in this patient, creating an new stop codon and was predicted to result in a truncated protein lacking normal POU3F4 transcription factor function. Conclusion： Through analysis of the POU3F4 gene and clinical manifestations in the patient, we conclude that a novel mutation may have resulted in a premature stop codon, contributing to the mutation of POU3F4 gene.
基金supported by the funding from the National High Technology Research and Development Program of China (863 Program) to Huijun Yuan (No.2007AA02E466)Key Project of National Natural Science Foundation of China to Huijun Yuan (Nos.81030017, 30571018) and Xuezhong Liu (No. 30528025)
文摘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 substitu- tion 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.
