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Jiang L.,Central South University | Jiang L.,Hunan Key Laboratory of Otolaryngology Critical Diseases | Liu Y.,Central South University | Liu Y.,University of South China | And 16 more authors.
Acta Oto-Laryngologica | Year: 2011

Conclusions: There could be another candidate gene in DFNA2, which could be responsible for the hearing loss phenotype. Objective: We collected a four-generation family from the southern part of China with autosomal dominant sensorineural hearing impairment. In order to identify the responsible pathogenic mutations in this family, we set out to identify the locus and to sequentially analyze the candidate genes in the identified region. Methods: After family ascertainment and clinical analysis, exclusive analysis was performed. Then a genome-wide scan was performed using an Illumina Linkage-12 DNA Analysis Kit (average spacing 0.58 cM). Fine-mapping markers were genotyped to identify the locus. Finally, we performed haplotype analyses and candidate gene DNA sequencing for the family. Results: The known genetic loci and genes were not associated with our family. The genome-wide scan and haplotype analyses traced the disease to chromosome 1p34.2-p34.3 with maximum multi-point LOD score of 3.2, which overlaps with DFNA2. We failed to identify any of the known or novel variants within KCNQ4, a voltage-gated potassium channel gene, and GJB3, a gene that encodes the gap junction protein connexin 31, which were the cloned deafness genes in DFNA2. © 2011 Informa Healthcare.

Jiang L.,Central South University | Jiang L.,Hunan Key Laboratory of Otolaryngology Critical Diseases | Chen H.,Central South University | Chen H.,Hunan Key Laboratory of Otolaryngology Critical Diseases | And 15 more authors.
Biochemical and Biophysical Research Communications | Year: 2011

Objective: We analyzed the clinical features and family-related gene mutations for the first two Chinese cases of type IV Waardenburg syndrome (WS4). Methods: Two families were analyzed in this study. The analysis included a medical history, clinical analysis, a hearing test and a physical examination. In addition, the EDNRB, EDN3 and SOX10 genes were sequenced in order to identify the pathogenic mutation responsible for the WS4 observed in these patients. Results: The two WS4 cases presented with high phenotypic variability. Two novel heterozygous mutations (c.254G>A and c.698-2A>T) in the SOX10 gene were detected. The mutations identified in the patients were not found in unaffected family members or in 200 unrelated control subjects. Conclusions: This is the first report of WS4 in Chinese patients. In addition, two novel mutations in SOX10 gene have been identified. © 2011.

Zhanga H.,Central South University | Zhanga H.,Hunan Provincial Tumor Hospital | Feng Y.,Central South University | Feng Y.,Hunan Key Laboratory of Otolaryngology critical diseases | And 8 more authors.
Journal of International Advanced Otology | Year: 2012

Objective: To investigate the mechanism of the deafness-causing mutation S448X in the pendrin protein through measurement of the expression levels and functional activities of the wild-type (WT) and mutant proteins. Materials and Methods: pEGFP N1 SLC26A4 S448X (S448X-EGFP) and wild-type pEGFP N1 SLC26A4 (WT-EGFP) were transfected into cos-7 cells and their expression detected by western blotting. Immunostaining and confocal microscopy were used to determine the subcellular localization of WT and S448X proteins. The effects of overexpression of WT and S448X pendrin on ion transport in the cell were measured by whole-cell patch clamp analysis. Results: S448X was expressed in the cytoplasm, and co-localized with the ER, while WT pendrin was efficiently transported to the cell membrane. The chloride ion current was significantly weaker (P < 0.05) in cells expressing the S448X mutant protein than those expressing the wild-type protein. Conclusion: The S448X mutation in pendrin could not be transported to the cell membrane after translation and remained in the endoplasmic reticulum (ER). This mutation had a reduced ability to transport chloride ions, suggesting that inhibition of chloride ion transport might lead to the pathologies associated with the S448X mutation. © 2005 The Mediterranean Society of Otology and Audiology.

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