Frequency of SMARCB1 mutations in familial and sporadic schwannomatosis

• DOI: 10.1007/s10048-012-0319-8
• Publication Date: 2012-03-22T17:34:02Z
• Authors: Miriam J. Smith; Andrew J. Wallace; Naomi L. Bowers; Cecilie F. Rustad; C. Geoff Woods; Guy D. Leschziner; Rosalie E. Ferner; D. Gareth R. Evans
• Keywords: 0303 health sciences; Skin Neoplasms; Neurofibromatoses; Chromosomal Proteins, Non-Histone; DNA Mutational Analysis; SMARCB1; Exons; SMARCB1 Protein; 3. Good health; Cohort Studies; DNA-Binding Proteins; 03 medical and health sciences; Schwannomatosis; NF2; Mutation; Humans; Genes, Tumor Suppressor; Genetic Predisposition to Disease; Genetic Testing; Neurilemmoma; Transcription Factors

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.