Lynch syndrome with MLH1 germline variant in an extended family: a case report.

Lynch syndrome (LS) is an inherited cancer predisposition syndrome associated with an increased risk of several malignancies, particularly colorectal cancer (CRC). The diagnosis of LS is typically based on family history and confirmed by genetic testing, most commonly involving pathogenic variants in mismatch repair genes, including MLH1, MSH2, MSH6, and PMS2. We report a proband who developed CRC at the age of 52 years and had a family history suggestive of LS. Immunohistochemical analysis revealed loss of MLH1 and PMS2 expression in the proband, and isolated loss of PMS2 expression in his maternal cousin. Whole-exome sequencing followed by Sanger sequencing identified a heterozygous MLH1 c.1652A>C (p.Asn551Thr) variant in the proband, his maternal cousin, and four additional affected family members. Based on the clinical, pathological, and genetic findings, the extended family was diagnosed with LS. Taken together, MLH1 c.1652A>C (p.N551T) variant may contribute to carcinogenesis, and its co-segregation with LS in this family provides supportive evidence for its potential pathogenicity.