[A Family Affected by Lynch Syndrome Caused by MSH6 Germline Mutation].

The clinical features of Lynch syndrome caused by MSH6 are not fully understood since very few cases have been described in Japan. We report 2 cases of Lynch syndrome with germline mutation of MSH6 in a family. Case 1: A 47-year-old man was referred to our department due to positive fecal occult blood test. He had family history of endometrial cancer and gastric cancer (mother), and bladder cancer (father). We performed sigmoidectomy for sigmoid cancer. The pathological findings revealed mucosal cancer (pTis, pN0, H0, P0, pStage 0). Since the patient met the revised Bethesda guidelines, we performed microsatellite instability (MSI) testing and immunohistochemistry for mismatch repair genes (MLH1, MSH2, MSH6, and PMS2) as screening for Lynch syndrome. MSI-high and loss of MSH6 were found. Based on these results, genetic testing of MSH6 revealed a frame-shift mutation in codon 604 (c. 1806-1809delAAG/p. Glu604LeufsX5). Case 2: The patient was a younger brother of case 1. The same mutation was detected in the MSH6 gene.