Abstract
BACKGROUND: Lynch syndrome (LS) is caused by mutations in DNA mismatch repair (MMR) genes, which accounts for 3-5% of colorectal cancer. The risks of several types of cancer are greatly increased among individuals with LS. In this study, 4 members of a Chinese family with a MLH1 pathogenic variant, resulting in colonic carcinoma, was reported. CASE PRESENTATION: A 52-year-old colon cancer female was brought to us with a family history of colon cancer. Genetic counseling traced 4 members in her family with colon cancer (mother and 3 siblings including the proband) as well as other cancer types. Next generation sequencing (NGS) with a multiple gene panel including MMR genes showed a germline mutation in MLH1 (c.1852_1854delAAG, p.K618del) in all 3 affected family members and confirmed the diagnosis of Lynch syndrome. In addition, this mutation was also identified in a asymptomatic offspring, who was then recommended to a prophylactic measure against cancer. A personalized health care plan was implemented for monitoring the condition and progression of the affected individuals. CONCLUSION: Based on public database searching followed by pedigree verification, p.K618del variant in MLH1 is a pathogenic mutation, which supported the diagnosis of LS. This case highlights the importance of diagnosis and management in patients with hereditary cancer syndromes, particularly for asymptomatic family members.