GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment

Background: Mutations in GJB2 are the most common molecular defects responsible for autosomal recessive nonsyndromic hearing impairment (NSHI). The mutation spectra of this gene vary among different ethnic groups. Methods: In order to understand the spectrum and frequency of GJB2 mutations in the Chinese population, the coding region of the GJB2 gene from 2063 unrelated patients with NSHI was PCR amplified and sequenced. Results: A total of 23 pathogenic mutations were identified. Among them, five (p.W3X, c.99delT, c.155_c.158delTCTG, c.512_c.513insAACG, and p.Y152X) are novel. Three hundred and seven patients carry two confirmed pathogenic mutations, including 178 homozygotes and 129 compound heterozygotes. One hundred twenty five patients carry only one mutant allele. Thus, GJB2 mutations account for 17.9% of the mutant alleles in 2063 NSHI patients. Overall, 92.6% (684/739) of the pathogenic mutations are frame-shift truncation or nonsense mutations. The four prevalent mutations; c.235delC, c.299_c.300delAT, c.176_c.191del16, and c.35delG, account for 88.0% of all mutantalleles identified. The frequency of GJB2 mutations (alleles) varies from 4% to 30.4% among different regions of China. It also varies among different sub-ethnic groups. Conclusion: In some regions of China, testing of the three most common mutations can identify at least one GJB2 mutant allele in all patients. In other regions such as Tibet, the three most common mutations account for only 16% the GJB2 mutant alleles. Thus, in this region, sequencing of GJB2 would be recommended. In addition, the etiology of more than 80% of the mutant alleles for NSHI in China remains to be identified. Analysis of other NSHI related genes will be necessary

Association between TGM5, PPAP2B and PSMA4 polymorphisms and NSCLC in never-smoking Chinese population

Aim: To explore the potential association between SNPs in transglutaminase 5 (TGM5), phosphatidic acid phosphatase type 2B (PPAP2B) and proteasome subunit, alpha type 4 (PSMA4) and non-small cell lung cancer (NSCLC) susceptibility in Chinese patients who were non-smokers. Setting and Design: A case-controlled study was conducted among Chinese population. Materials and Methods: Two hundred NSCLC patients and 200 healthy controls who were age and sex matched were genotyped for rs504417 of TGM5, rs1261411 of PPAP2B and rs7164594 of PSMA4. Genotyping was performed using the Sequenom MassARRAY system based on the chip-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry platform. Statistical Analysis Used: The association between genotype and lung cancer risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses. Results: There was no significant difference for the TGM5 rs504417, PPAP2B rs1261411 and PSMA4 rs716459 in allele or genotype frequencies, whether between controls and NSCLC or between controls and subgroups. Conclusions: polymorphisms of TGM5, PPAP2B and PSMA4 are not major contributors to NSCLC susceptibility, this primarily be attributed to the significantly distinct genetic background of Asian populations from western populations