Molecular and clinical analyses of 84 patients with tuberous sclerosis complex.
BACKGROUND
Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of multiple hamartomas in many internal organs. Mutations in either one of 2 genes, TSC1 and TSC2, have been attributed to the development of TSC. More than two-thirds of TSC patients are sporadic cases, and a wide variety of mutations in the coding region of the TSC1 and TSC2 genes have been reported.


METHODS
Mutational analysis of TSC1 and TSC2 genes was performed in 84 Taiwanese TSC families using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing.


RESULTS
Mutations were identified in a total of 64 (76 %) cases, including 9 TSC1 mutations (7 sporadic and 2 familial cases) and 55 TSC2 mutations (47 sporadic and 8 familial cases). Thirty-one of the 64 mutations found have not been described previously. The phenotype association is consistent with findings from other large studies, showing that disease resulting from mutations to TSC1 is less severe than disease due to TSC2 mutation.


CONCLUSIONS
This study provides a representative picture of the distribution of mutations of the TSC1 and TSC2 genes in clinically ascertained TSC cases in the Taiwanese population. Although nearly half of the mutations identified were novel, the kinds and distribution of mutation were not different in this population compared to that seen in larger European and American studies.
Hung
Chia-Cheng
CC
Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan. r91548020@ntu.edu.tw
Su
Yi-Ning
YN
Chien
Shu-Chin
SC
Liou
Horng-Huei
HH
Chen
Chih-Chuan
CC
Chen
Pau-Chung
PC
Hsieh
Chia-Jung
CJ
Chen
Chih-Ping
CP
Lee
Wang-Tso
WT
Lin
Win-Li
WL
Lee
Chien-Nan
CN
D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D013624:Taiwan; D014402:Tuberous Sclerosis / Q000175:diagnosis* / 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