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GENATLAS PHENOTYPE
last update : 13/11/2008
Symbol CMMRD
Location 3p21, 2p21, 2p16, 7p22
Name constitutional mismatch repair-deficiency syndrome
Other name(s) brain tumor-polyposis syndrome, Turcot syndrome
Corresponding gene MLH1 , MSH2 , MSH6 , PMS2
Other symbol(s) SNTCL, BTPS1
Main clinical features
  • more severe phenotype than monoallelic MMR genes mutations, with development of childhood cancers, mainly haematological malignancies and/or brain tumours, as well as early-onset colorectal cancers and signs reminiscent of neurofibromatosis type 1, mainly café au lait spots, in almost all patients
  • associated in anu cases with agenesis of the corpus callosum and gray matter heterotopia (PMID: 22692065))
    • Genetic determination autosomal recessive
    Function/system disorder multisystem/generalized
    Type malignancy
    Remark(s)
  • biallelic mutations in mismatch repair (MMR) genes whose monoallelic mutations cause Lynch syndrome
  • amino acid substitutions in the connector (G566R) and lever (D803G and V878A) domains of MSH6 disrupt proper coordination of nucleotide processing with DNA binding, suggesting that the allosteric signaling between the distant sites in the heterodimer is affected (significant conformational change occurs in MSH2-MSH6 upon binding to DNA and nucleotides that is likely to be crucial for proper coordination of downstream events in MMR)