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

Area of Science:

• Genetics
• Oncology
• Gastroenterology

Background:

• Lynch syndrome is an inherited disorder increasing cancer risk.
• Clinical manifestations of Lynch syndrome due to MSH6 mutations are poorly characterized in Japan.
• Limited case reports highlight the need for further research.

Observation:

• Two male patients from the same family in Japan were diagnosed with Lynch syndrome.
• Case 1 presented with sigmoid cancer and a family history of endometrial, gastric, and bladder cancers.
• Screening revealed microsatellite instability-high (MSI-high) status and MSH6 protein loss in Case 1.

Findings:

• Germline genetic testing identified a novel frame-shift mutation (c.1806-1809delAAG/p.Glu604LeufsX5) in the MSH6 gene in both patients.
• This specific MSH6 mutation was confirmed in the affected brother (Case 2).
• The findings confirm MSH6 as a causative gene for Lynch syndrome in this Japanese family.

Implications:

• This report expands the understanding of MSH6 mutations and their associated clinical features in Lynch syndrome.
• Early identification of MSH6 mutations can facilitate timely genetic counseling and cancer surveillance.
• Further research is warranted to elucidate the full spectrum of MSH6-related Lynch syndrome phenotypes.