The PMS2 gene is a mismatch repair gene that was identified as a colon cancer risk gene on chromosome 7 in 1994 (Nicolaides 1994; Liu 2001). Deleterious germline mutations in PMS2 make up less than 5% of cases of Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (Peltomaki 2003). Individuals with Lynch syndrome due to PMS2 mutations have an increased risk of colon cancer and endometrial cancer, and they may have an increased risk of other cancers, including ovarian cancer, stomach cancer, small bowel cancers, brain cancer, and urinary tract cancers (Senter 2008). Please visit the Lynch Syndrome GeneReviews page for more information.
Individuals with biallelic (homozygous or compound heterozygous) mutations in PMS2 can present with constitutional mismatch repair deficiency, an autosomal recessive disorder characterized by childhood-onset hematological, brain, and colorectal malignancies, along with café-au-lait spots, Lisch nodules, and other clinical features overlapping with neurofibromatosis 1 (Felton 2007; Wimmer 2010).
Affected Phenotypes Included in Penetrance Model
Grouped small bowel cancer
Stomach or gastric cancer
Urinary tract cancers (excluding bladder)
Note: Diagnoses other than those listed above, such as breast cancer, prostate cancer, and pancreatic cancer, are not included in this model.
Coding the Pedigree
Code affected individuals in column 5 of the Excel or plain text file used to build your pedigree.
- Code "2" (affected) for individuals with any of the diagnoses in the affected list.
- Code "1" (unaffected) for individuals who have not had any of the diagnoses in the affected list. Individuals with only breast cancer. prostate cancer, and/or pancreatic cancer should be coded as "1."
- Code "0" for individuals with uncertain or unknown affected status.
More information on formatting pedigrees can be found here.
Penetrance classes for PMS2
Penetrance is gender-specific.
|Age Range||Homozygous Normal||Heterozygous||Homozygous Normal||Heterozygous|
- Nicolaides NC, et al. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature. 1994, 371:75. PMID: 8072530
- Liu T, et al. The role of hPMS1 and hPMS2 in predisposing to colorectal cancer. Cancer Res. 2001, 61:7798. PMID: 11691795
- Peltomaki P. Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol. 2003, 21:1174. PMID: 12637487
- Senter L, et al. The clinical phenotype of Lynch syndrome due to germline PMS2 mutations. Gastroenterology. 2008, 135:419. PMID: 18602922
- Felton KEA, et al. Constitutive deficiency in DNA mismatch repair. 2007, 71:483. PMID: 17539897
- Wimmer K, et al. Constitutional mismatch repair-deficiency syndrome. 2010, 95:699. PMID: 20442441