Mutational analysis of TSC1 and TSC2 in Korean patients with tuberous sclerosis complex.
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by a broad phenotypic spectrum that includes seizures, mental retardation, renal dysfunction and dermatological abnormalities. TSC is caused by mutations affecting either of the tumor-suppressor genes TSC1 and TSC2. At least 495 mutations of TSC1 and TSC2 have been reported. Twenty-two males and 22 females who were diagnosed with TSC at the Seoul National University Children's Hospital between 1982 and 2002 were enrolled in the study. Forty-four patients were from different families and included nine familial cases and 35 sporadic cases. Denaturing high performance liquid chromatography and DNA sequencing analysis of TSC1 and TSC2 revealed 13 types of mutations (30%). One novel mutation of TSC1 and nine novel mutations of TSC2 were identified. The TSC1 mutation and one of the nine TSC2 mutations were missense mutations and seven of the nine TSC2 mutations caused truncation of proteins. One novel single nucleotide substitution was identified at the consensus splicing donor site of exon 39 (c.5,069-1G>A). This mutation is predicted to cause a splicing error. Of the TSC2 mutation loci, the correlation with cardiac rhabdomyoma was more significant when the mutation was in the C-terminal part of tuberin than the N-terminal part. This is the first extensive mutational analysis of TSC1 and TSC2 in Korean TSC patients.
Choi
Ji-Eun
JE
Department of Pediatrics, Borame Hospital affiliated to Seoul National University Hospital, 395 shindaebang-2-dong, Dongjak-gu, 156-707 Seoul, South Korea. jieunchoi6647@hanmail.net
Chae
Jong-Hee
JH
Hwang
Yong-Seung
YS
Kim
Ki-Joong
KJ
D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D007723:Korea; D008297:Male; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014402:Tuberous Sclerosis / Q000145:classification / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins