High-grade brain tumors in siblings with biallelic MSH6 mutations

Pediatr Blood Cancer. 2011 Dec 1;57(6):1067-70. doi: 10.1002/pbc.23217. Epub 2011 Jun 14.


Biallelic germline mutations of Constitutional mismatch repair-deficiency syndrome (CMMR-D) genes, MLH1, MSH2, MSH6, and PMS2 are characterized by increased risk of childhood malignancy. We report a case with CMMR-D caused by novel homozygous MSH6 mutations leading to gliomatosis cerebri and T-ALL in an 11-year-old female and glioblastoma multiforme in her 10-year-old brother, both with rapid progression of the diseases. A literature review on brain tumors in CMMR-D families shows that they are treatment-resistant and lead to early death. Identification of patients with CMMR-D is critical, and specific cancer screening programs with early surgery are recommended.

Publication types

  • Case Reports

MeSH terms

  • Alleles*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Child
  • DNA Repair-Deficiency Disorders / genetics*
  • DNA Repair-Deficiency Disorders / pathology
  • DNA-Binding Proteins / genetics*
  • Female
  • Glioblastoma / genetics
  • Humans
  • Male
  • Mutation*
  • Pedigree
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Siblings*


  • DNA-Binding Proteins
  • G-T mismatch-binding protein