A new subtype of Lynch syndrome associated with c.354T>A (p. Y118*) identified in a Chinese family: case report and literature review.

Background: Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by mutations in mismatch repair genes. Genetic counseling is crucial for the prevention and treatment of LS, as individuals with these mutations have an increased lifetime risk of developing multiple cancers. MutS Homolog 2 () is a protein-coding gene that plays a key role in LS. A significant number of LS cases are linked to harmful heterozygous mutations in the gene.

Case Presentation: The proband was a 50-year-old endometrial dedifferentiated carcinoma patient with a dMMR/MSI-H tumor negative for / expression by immunohistochemistry. Genetic counseling and tumor gene testing were conducted using next-generation sequencing (NGS) technology, which revealed a previously unknown germline gene nonsense mutation NM_000251.2:exon2.354T>A (p.Y118*), leading to a diagnosis of LS. Further analysis of this variant in five family members of the patient confirmed its presence in all individuals, with one family member being diagnosed with colorectal cancer (CRC) at the age of 43. The proband received postoperative chemoradiotherapy and achieved a disease-free survival of 2 years, with ongoing follow-up.

Conclusion: This study provides evidence that the nonsense mutation c.354T>A is a highly likely pathogenic mutation and is responsible for typical LS-associated endometrial carcinoma. It emphasizes the importance of genetic counseling for proband family members to facilitate early diagnosis of LS-related carcinoma.