Tuberous Sclerosis Complex in Chinese patients: Phenotypic analysis and mutational screening of TSC1/TSC2 genes.

PURPOSE: Tuberous sclerosis complex (TSC) is characterized by the development of hamartomas in multiple organ systems. This study attempted to screen mutations and to investigate the mutation distribution and related phenotypes including epilepsy of Chinese TSC patients. METHODS: We performed the genotypic analysis of TSC1 and TSC2 genes in 77 unrelated Chinese TSC patients using direct Sanger sequencing and Multiplex ligation-dependent probe amplification (MLPA). RESULTS: Mutations were identified in a total of 63 (81.8%) cases, including 18 TSC1 mutations (8 nonsense mutations, 6 frameshift, 1 in-frame shift, 1 missense and 2 splice-site) and 45 TSC2 mutations (13 missense, 3 nonsense, 6 splicing, 6 in-frame shift,12 frameshift mutations and 5 large deletions). Large deletions were presented exclusively in TSC2 gene, accounting for 7.9% of all mutations in this study. Fourteen novel mutations were identified in this study. CONCLUSIONS: Epilepsy occurs in approximately 75.3% (58/77) of patients. Hypomelanotic macules occurred significantly more often in patients with TSC2 mutations and cases with TSC1/TSC2 mutations had a significantly higher frequency of cortical nodule than patients with no mutations identified. Overall, our data expands the spectrum of mutations associated with the TSC loci and will be of value to the genetic counseling in patients with the disease.

[Prevalence of CYP2C19 polymorphisms involved in clopidogrel metabolism in Fujian Han population].

OBJECTIVE: To investigate the frequency of CYP2C19 polymorphisms involved in clopidogrel metabolism in Fujian Han population. METHODS: Frequencies of CYP2C19* 2, CYP2C19*3 and CYP2C19*17 in 1001 unrelated Fujian Han volunteers were determined with polymerase chain reaction-restriction fragment length polymorphism and direct sequencing method. RESULTS: The frequencies of CYP2C19*2, *3 and *17 were 32.4%, 5.8% and 0.4%, respectively. According to genotyping results, intermediate metabolizers (CYP2C19 *1/*2 or *1/*3) and poor metabolizers (CYP2C19 *2/*2 and *2/*3) respectively accounted for 47.95% and 13.99% of all subjects. Above frequencies were similar to those of Japan, Korea, Singapore, Malaysia, Thailand and Chinese Dai, Mongolian,Li and Hui ethnics (P>0.05), but were significantly different from those of Chinese Kazakh and Uygur ethnics, and people from Iran, Russia, Italy, Poland, Norway, Canada native Indians, Bolivia, Egypt or Tanzania (P<0.05). CONCLUSION: Ethnic/regional diversity exist with regard to the prevalence of CYP2C19 polymorphisms. No significant difference were found between Fujian Han Chinese and Dai, Mongolian, Li and Hui from China or other populations from East and Southeast Asia, but higher frequencies of intermediate metabolizers and poor metabolizers compared with populations of Kazakh and Uygur in China, and people from Europe, South America and Africa.