Abstracts

Tuberous sclerosis (TS) is an autosomal dominant neurocutaneous syndrome, characterized by multi-systemic hamartomatous lesions. More than 450 causable aberrations in TSC1 and TSC2, encoding hamartin and tuberin, were reported, but their phenotypic correlation is not clarified. We analyze mutations of TSC1 and TSC2 in clinically diagnosed TS patients, and investigate genotype/phenotype correlation.
Forty four patients (22 males, 22 females) were included, who met the criteria of definitive tuberous sclerosis complex by Tuberous Sclerosis Consensus Conference. Nine patients (20%) were familial cases. Genomic DNA was extracted from patients[rsquo] blood samples, and exons of TSC1 and TSC2 were PCR-amplified. Mutation screening was performed by denaturing high performance liquid chromatography (DHPLC), and confirmed by direct sequencing. Genotype-phenotype correlation was analyzed.
Among 44 patients, 41 patients (93%) suffered from seizure. Hypopigmented macules were noted in 35 patients (80%), facial angiofibromatosis in 25 patients (57%), and Shagreen[rsquo]s patch in 14 patients (32%). On brain MRI, subependymal nodules were revealed in 40 patients (91%), cortical tubers in 34 patients (83%), and giant cell astrocytoma in 3 patients (7%). In 13 patients (30%), renal cysts were identified. Renal and hepatic angiomyolipoma were noted in 3 patients (7%), and 2 patients (5%) respectively. No significant difference was proved between familial and sporadic cases. Mutations were identified in 13 of 44 cases (30%), composed of two mutations in TSC1 (5%) and eleven mutations in TSC2 (25%). Mutation types were as follows: 5 deletions (39%), 4 nonsense mutations (31%), 3 missense mutations (23%), and 1 insertion (8%). Eleven were novel mutations. Mutations in C-terminal half of TSC2 (amino acid 1100-1805) had significant correlation with cardiac rhabdomyoma than those in N-terminal half (amino acid 1-1099). Other clinical features did not show genotype-phenotype correlation.
These data provide the first representative features of distribution and spectrum of TSC1 and TSC2 mutations in Korean patients. In our study, TSC1 and TSC2 mutation rates were relatively lower than mutation rate reported in western countries. Eleven novel mutations were identified in our study.