1. Mild Epilepsy Phenotype in TSC2 Patients with Codon 905 Mutations
- Author
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Anna Jansen, Sancak, O., D Agostino, M. D., Badhwar, A., Roberts, P., Gobbi, G., Wilkinson, R., Melanson, D., Koenekoop, R., Gans, M., Den Ouweland, A. M. W., Nellist, M., Pandolfo, M., Sims, K., Thiele, E., Andermann, F., Dubeau, F., Kwiatkowski, D., Halley, D. J. J., Andermann, E., and Public Health Care
- Subjects
epilepsy ,TSC2 patients - Abstract
Purpose: To report the epilepsy phenotype, the clinical manifestations, and functional aspects of codon 905 mutations in tuberous sclerosis type 2 (TSC2). Methods: We carried out a detailed study of the TSC phenotype in a large French-Canadian family (Family A). Linkage analysis of the TSC loci and mutation analysis of the TSC2 gene were performed. In addition, clinical and molecular data on three families and six sporadic patients with a mutation at the same codon were collected. The functions of the codon 905 mutations were studied and related to the phenotype. Results: A 2714G>A (R905Q) missense mutation in exon 23 of TSC2 was identified in 25 individuals in Family A. The mild TSC phenotype in this family was characterised by the absence of cortical tubers, intractable epilepsy, disfiguring skin lesions, severe mental retardation or other major organ involvement. Diagnostic criteria were met in only a minority of family members, delaying diagnosis. Three other families with the same mutation were found to have a similar mild phenotype. Six patients with a different mutation at the same codon (2713G>T or R905W) had a more severe phenotype. Functional studies of the R905Q/R905W mutated tuberin demonstrated only a mild impact on tuberin function. Conclusion: We have described ten new families with mild TSC2 phenotypes, all of which had codon 905 mutations. The epilepsy phenotype was unusually mild, characterised mainly by seizures that remitted spontaneously or were easily controlled with anti-epileptic drugs. Functional studies showed a minimal effect of the R905Q/W mutation on tuberin function. Genotype-phenotype correlations among families with R905Q and R905W were carried out.
- Published
- 2005