Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas

Nat Genet. 2013 Mar;45(3):295-8. doi: 10.1038/ng.2552. Epub 2013 Feb 3.


One-third of all primary central nervous system tumors in adults are meningiomas. Rarely, meningiomas occur at multiple sites, usually occurring in individuals with type 2 neurofibromatosis (NF2). We sequenced the exomes of three unrelated individuals with familial multiple spinal meningiomas without NF2 mutations. We identified two individuals with heterozygous loss-of-function mutations in the SWI/SNF chromatin-remodeling complex subunit gene SMARCE1. Sequencing of SMARCE1 in six further individuals with spinal meningiomas identified two additional heterozygous loss-of-function mutations. Tumors from individuals with SMARCE1 mutations were of clear-cell histological subtype, and all had loss of SMARCE1 protein, consistent with a tumor suppressor mechanism. Our findings identify multiple-spinal-meningioma disease as a new discrete entity and establish a key role for the SWI/SNF complex in the pathogenesis of both meningiomas and tumors with clear-cell histology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Deletion
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Loss of Heterozygosity
  • Male
  • Meningeal Neoplasms* / genetics
  • Meningeal Neoplasms* / pathology
  • Meningioma* / genetics
  • Meningioma* / pathology
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Neurofibromatosis 2 / genetics
  • Neurofibromatosis 2 / metabolism
  • Polymorphism, Single Nucleotide


  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • SMARCE1 protein, human

Associated data

  • RefSeq/NM_003079
  • RefSeq/NP_003070