Constitutional mismatch repair deficiency: a case on a commonly misinterpreted mutation in colon cancer

Abstract

It is estimated that 153,020 cases of CRC per year, with an increase in diagnoses in younger patients. We present a case of a female with an early presentation of Lynch Syndrome and CRC, who, on her third malignant presentation, was re-diagnosed as a constitutional mismatch repair deficiency.

Keywords: Colorectal cancer; HNPCC; Lynch syndrome; Mismatch repair.

Fig. 1

Repair sequence in DNA mismatch. 1) MutSα recognizes and binds a DNA mismatch. 2) MutSα-ATP/dependant conformational change. 3) Recruitment of PCNA. 4) PMS2 breaks a single strand and recruits Exo1. 5) Exo1 removes mismatch base/segment. 6) Polymerase δ synthetase the missing base/segment. These sequences, when abnormal, as in the patient of discussion, result in accumulation of mutations further increasing the risk of neoplasms

Fig. 2

CT scan of the abdomen with IV contrast. It showed an annular lesion in the Jejunum (Image on the left with the red arrow at transition point), signaling as the cause of SBO (proximal dilation of SB loops as pointed by the arrow at the right image)

Fig. 3

Small-bowel mass following small-bowel resection:- Adenocarcinoma, G2, moderately differentiated, 5.5 cm in greatest dimension, invading through the muscularis propria into the subserosa.- Lymphovascular invasion present.- All margins negative for invasive carcinoma

Fig. 4

Genetic transmission of MMR mutations. To acquire HNPCC, recipient must receive one mutated copy of AD MMR mutation. CMMR-D offspring require two copies of mutated gene as they are inherited in AR fashion. The patient at discussion has parents that must both contain mutations in repair genes to have an established diagnosis of CMMR-D. [3]