title: Novel mutations in 21 patients with tuberous sclerosis complex and variation of tandem splice-acceptor sites in TSC1 exon 14.
abstract: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by epilepsy, mental retardation, skin lesions, and tumors in various organs. However, TSC is sometimes difficult to diagnose because of its broad phenotypic spectrum. In such cases, it is essential to find a mutation in the disease-causing genes, TSC1 and TSC2. In this study, we analyzed 21 TSC patients from 16 families using a combination method of DHPLC and nucleotide sequencing. We identified 16 novel mutations in the 16 families: nine mutations in TSC1 (1 insertion, 7 deletion and 1 nonsense mutations) and seven mutations in TSC2 (2 insertion, 2 deletion, 1 missense mutations and 2 splicing abnormalities). We also tested the possibility of very short alternative splicing due to a variation of the tandem splice-acceptor sites of TSC1 exon 14 in a patient. RT-PCR and sequencing analysis indicated that no alternative splicing occurred in the patient. In conclusion, we confirmed the diagnosis of all patients using mutation analysis and clarified that variation of the tandem splice-acceptor sites in TSC1 exon 14 does not cause a splicing abnormality.
authors.affiliation: Department of Genetic Epidemiology, Graduate School of Medicine, Kobe University, Japan. teguhharyosasongko@yahoo.com
authors.forename: Teguh Haryo
authors.initials: TH
authors.lastname: Sasongko
authors.forename: Mari
authors.initials: M
authors.lastname: Wataya-Kaneda
authors.forename: Keiko
authors.initials: K
authors.lastname: Koterazawa
authors.lastname: Gunadi
authors.forename: Surini
authors.initials: S
authors.lastname: Yusoff
authors.forename: Indra Sari Kusuma
authors.initials: IS
authors.lastname: Harahap
authors.forename: Myeong Jin
authors.initials: MJ
authors.lastname: Lee
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
authors.forename: Hisahide
authors.initials: H
authors.lastname: Nishio
mesh_terms: D000483:Alleles; D001483:Base Sequence; D005091:Exons / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D009711:Nucleotides / Q000235:genetics; D022821:RNA Splice Sites / 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 / Q000235:genetics*
chemical_list: D009711:Nucleotides; D022821:RNA Splice Sites; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins