Frequency of SMARCB1 mutations in familial and sporadic schwannomatosis

Neurogenetics. 2012 May;13(2):141-5. doi: 10.1007/s10048-012-0319-8. Epub 2012 Mar 22.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomal Proteins, Non-Histone / genetics*
  • Cohort Studies
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Exons / genetics
  • Genes, Tumor Suppressor
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Mutation / genetics*
  • Neurilemmoma / genetics*
  • Neurofibromatoses / genetics*
  • SMARCB1 Protein
  • Skin Neoplasms / genetics*
  • Transcription Factors / genetics*

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors

Supplementary concepts

  • Schwannomatosis