RGD Reference Report - Evidence for a recessive inheritance of Turcot's syndrome caused by compound heterozygous mutations within the PMS2 gene. - Rat Genome Database

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Evidence for a recessive inheritance of Turcot's syndrome caused by compound heterozygous mutations within the PMS2 gene.

Authors: De Rosa, M  Fasano, C  Panariello, L  Scarano, MI  Belli, G  Iannelli, A  Ciciliano, F  Izzo, P 
Citation: De Rosa M, etal., Oncogene. 2000 Mar 23;19(13):1719-23.
RGD ID: 1599141
Pubmed: PMID:10763829   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.onc.1203447   (Journal Full-text)

Turcot's syndrome is a genetic disease characterized by the concurrence of primary brain tumors and colon cancers and/or multiple colorectal adenomas. We report a Turcot family with no parental consanguinity, in which two affected sisters, with no history of tumors in their parents, died of a brain tumor and of a colorectal tumor, respectively, at a very early age. The proband had a severe microsatellite instability (MIN) phenotype in both tumor and normal colon mucosa, and mutations in the TGFbeta-RII and APC genes in the colorectal tumor. We identified two germline mutations within the PMS2 gene: a G deletion (1221delG) in exon 11 and a four-base-pair deletion (2361delCTTC) in exon 14, both of which were inherited from the patient's unaffected parents. These results represent the first evidence that two germline frameshift mutations in PMS2, an MMR gene which is only rarely involved in HNPCC, are not pathogenic per se, but become so when occurring together in a compound heterozygote. The compound heterozygosity for two mutations in the PMS2 gene has implications for the role of protein PMS2 in the mismatch repair mechanism, as well as for the presymptomatic molecular diagnosis of at-risk family members. Furthermore, our data support and enlarge the notion that high DNA instability in normal tissues might trigger the development of cancer in this syndrome.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PMS2HumanBrain Neoplasms  IAGP  RGD 
Pms2RatBrain Neoplasms  ISOPMS2 (Homo sapiens) RGD 
Pms2MouseBrain Neoplasms  ISOPMS2 (Homo sapiens) RGD 
PMS2HumanColonic Neoplasms  IAGP  RGD 
Pms2RatColonic Neoplasms  ISOPMS2 (Homo sapiens) RGD 
Pms2MouseColonic Neoplasms  ISOPMS2 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pms2  (PMS1 homolog 2, mismatch repair system component)

Genes (Mus musculus)
Pms2  (PMS1 homolog2, mismatch repair system component)

Genes (Homo sapiens)
PMS2  (PMS1 homolog 2, mismatch repair system component)


Additional Information