Variable expressivity and novel PTEN mutations in Cowden syndrome

Area of Science:

• Genetics
• Oncology
• Dermatology

Background:

• Cowden syndrome (CS) is a PTEN-associated disorder.
• Characterized by mucocutaneous hamartomas and increased cancer risk.

Observation:

• Reported an isolated CS case with fibrocystic breast disease, thyroid nodules, and facial/oral papillomas due to a novel PTEN nonsense mutation (c.940 G>T).
• Investigated a family with CS, including erythema nodosum, duodenal ulcer, intestinal polyps, and early-onset breast cancer.
• Identified an intronic PTEN mutation (c.1026+32 T>G) in the family, creating a new splice site.

Findings:

• Confirmed PTEN gene involvement in Cowden syndrome.
• Demonstrated variable clinical expressivity of CS, even within families.
• Identified two distinct PTEN mutations associated with CS phenotypes.

Implications:

• Understanding PTEN mutations is crucial for CS diagnosis and management.
• Highlights the importance of genetic counseling for families with CS.
• Further research into PTEN's role in tumorigenesis is warranted.