Abstract
Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare autosomal recessive predisposition to colorectal polyposis and other malignancies, often childhood-onset, that is caused by biallelic inheritance of mutations in the same mismatch repair gene. Here, we describe a patient with a clinical diagnosis of CMMRD based on colorectal polyposis and young-onset endometrial cancer who was identified to have two alterations in trans in PMS2: one known pathogenic mutation (c.1831insA; p.Ile611Asnfs*2) and one novel variant of uncertain significance (c.505C>G; p.Arg169Glu), a missense alteration. We describe the clinical and molecular features in the patient harboring this novel alteration c.505C>G, who meets clinical criteria for CMMRD and exhibits molecular evidence supporting a diagnosis of CMMRD. Although experimental validation is needed to confirm its pathogenicity, PMS2 c.505C>G likely has functional consequences that contributes to our patient’s phenotype based on the patient’s clinical presentation, tumor studies, and bioinformatics analysis.
Original language | English (US) |
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Pages (from-to) | 587-591 |
Number of pages | 5 |
Journal | Familial Cancer |
Volume | 15 |
Issue number | 4 |
DOIs | |
State | Published - Oct 1 2016 |
Keywords
- Constitutional mismatch repair deficiency
- Lynch syndrome
- Variant of uncertain significance
ASJC Scopus subject areas
- Genetics
- Oncology
- Genetics(clinical)
- Cancer Research