title: Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex.
abstract: We have surveyed the mutations of TSC1 and TSC2 from 38 (25 sporadic, 11 familial, and 2 unknown) Japanese patients with tuberous sclerosis complex. In 23 of 38 subjects, we detected 18 new mutations in addition to 4 mutations that had been previously reported. We also found 3 new polymorphisms. The mutations were not clustered on a particular exon in either of the genes. Seven TSC1 mutations found in 3 familial and 4 sporadic cases were on the exons (3 missense, 2 nonsense point mutations, a 1-base insertion, and a 2-bp deletion). Fifteen TSC2 mutations were found in 5 familial cases, 10 sporadic cases, and 1 unknown case. The 12 mutations were on the exons (8 missense, 1 nonsense point mutations, a 1-bp insertion, a 5-bp deletion, and a 4-bp replacement) and 3 point mutations were on the exon-intron junctions. Although the patients with TSC2 mutations tend to exhibit relatively severe mental retardation in comparison to those with TSC1 mutations, a genotype-phenotype correlation could not yet be established. The widespread distribution of TSC1/TSC2 mutations hinders the development of a simple diagnostic test, and the identification of individual mutations does not provide the prediction of prognosis.
authors.affiliation: Gene Research Center, Tottori University, Yonago, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: E
authors.initials: E
authors.lastname: Nanba
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Ninomiya
authors.forename: K
authors.initials: K
authors.lastname: Ohno
authors.forename: M
authors.initials: M
authors.lastname: Mizuguchi
authors.forename: K
authors.initials: K
authors.lastname: Takeshita
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D014402:Tuberous Sclerosis / Q000235:genetics* / Q000473:pathology*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D011506:Proteins; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins