Which of the following Lynch syndrome (HNPCC) genes, when mutated, accounts for the highest proportion of Lynch syndrome cases?
- A MSH6
- B PMS2
- C MLH1 ✓
- D MSH2
Correct answer: C. MLH1
Explanation
MLH1 mutations account for approximately 40–50% of Lynch syndrome families, making it the most commonly mutated mismatch repair gene. MSH2 accounts for ~25–40%, MSH6 for ~7–10%, and PMS2 for ~5%. MLH1 and MSH2 mutations are associated with higher penetrance and greater colorectal cancer risk compared to MSH6 and PMS2. Loss of MLH1 can also occur by somatic promoter methylation in sporadic microsatellite-unstable colorectal cancers.
Reference: Bailey & Love's Short Practice of Surgery, 27th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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