Frequency of SMARCB1 mutations in familial and sporadic schwannomatosis

Neurogenetics - Tập 13 - Trang 141-145 - 2012
Miriam J. Smith1, Andrew J. Wallace1, Naomi L. Bowers1, Cecilie F. Rustad2, C. Geoff Woods3, Guy D. Leschziner4, Rosalie E. Ferner4, D. Gareth R. Evans1
1Department of Genetic Medicine, St Mary’s Hospital, Manchester Academic Health Sciences Centre (MAHSC), University of Manchester, Manchester, UK
2Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
3Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
4Guy’s and St Thomas’ NHS Foundation Trust, London, UK

Tóm tắt

Mutations of the SMARCB1 gene have been implicated in several human tumour predisposing syndromes. They have recently been identified as an underlying cause of the tumour suppressor syndrome schwannomatosis. There is a much higher rate of mutation detection in familial disease than in sporadic disease. We have carried out extensive genetic testing on a cohort of familial and sporadic patients who fulfilled clinical diagnostic criteria for schwannomatosis. In our current cohort, we identified novel mutations within the SMARCB1 gene and detected several mutations that have been previously identified in other schwannomatosis cohorts. Of the schwannomatosis screens reported to date, including our current dataset, SMARCB1 mutations have been found in 45 % of familial probands and 7 % of sporadic patients. The exon 1 mutation, c.41C >A, and the 3′ untranslated region mutation, c.*82C >T, are the most common changes reported in schwannomatosis disease so far, indicating mutation hotspots at both 5′ and 3′ portions of the gene. SMARCB1 mutations are found in a significant proportion of schwannomatosis patients, but there remains the possibility that further causative genes remain to be found.

Tài liệu tham khảo

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