81000145

open access

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Novel Mutations in 21 Patients with Tuberous Sclerosis Complex and Variation of Tandem Splice-acceptor Sites in TSC1 exon 14

English (英語)

The Kobe journal of the medical sciences

54(1)

73-81

Kobe University School of Medicine

2008

2008-02-20

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterizedby epilepsy, mental retardation, skin lesions, and tumors in various organs. However,TSC is sometimes difficult to diagnose because of its broad phenotypic spectrum. Insuch cases, it is essential to find a mutation in the disease-causing genes, TSC1 andTSC2. In this study, we analyzed 21 TSC patients from 16 families using a combinationmethod of DHPLC and nucleotide sequencing. We identified 16 novel mutations in the16 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 2splicing abnormalities). We also tested the possibility of very short alternative splicingdue 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 thepatient. In conclusion, we confirmed the diagnosis of all patients using mutationanalysis and clarified that variation of the tandem splice-acceptor sites in TSC1 exon 14does not cause a splicing abnormality.

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