A novel mutation of GJB6 in Chinese sporadic non-syndromic hearing impairment / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the contribution of the GJB6 gene [encoding connexin 30 (C?30)] mutations in Chinese population with sporadic non-syndromic hearing impairment. METHODS PCR reactions were performed with two pair of primers for the coding sequence of GJB6 gene and for the deletion of GJB6. PCR products bidirectional sequencing was subsequently applied in 214 patients with hearing loss and 86 normal controls. RESULTS A novel heterozygous mutation-233(C→A) was found, which results in amino acid change, A78D. This mutation wasn't detected in the control subjects. The altered valine residue lies within the second conserved transmembrane domain. The large deletion△(GJB6/ D13S1830)] of GJB6 was not found in this group. CONCLUSION The large deletion of GJB6 was not found in the Chinese deafness population. A novel heterozygous mutation of GJB6 was found. These results indicated GJB6 mutations are not a major cause of hearing loss in the Chinese population.

Positional cloning in Chinese X-linked congenital inner ear malformation family / 中国耳鼻咽喉头颈外科

OBJECTIVE This study aimed at identifying inner ear malformation underlying molecular determinant(s) using a large five-generation Chinese family with multiple familial cases. METHODS Model-based genetic linkage analyses were performed with the use of microsatellite polymorphisms to determine the disease locus. Mutation screening was performed with the family and unrelated population-based controls to establish molecular evidence that caused the specific X-linked inheritance pattern in the family. RESULTS Clinical investigations of the pedigree demonstrated the extremely high penetrance in the male members, but no penetrance in the female members. Linkage analyses mapped the disease to the chromosomal region Xq13.1-Xq23 (maximum X-linkage LOD score = 3.27). Mutation screening of the candidate genes in the linkage region by direct sequencing revealed a de novo missense substitution (925T→C) in the well-known deaf gene POU3F4. Direct sequencing on 110 unrelated controls did not detect any mutation. CONCLUSION a novel mutation of POU3F4 gene was identified to be the causative reason for the hearing loss in family with inner ear malformation.