Novel Mutations in Serbian MEN1 Patients: Genotype-phenotype Correlation

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer syndrome.
• MEN1 is characterized by primary hyperparathyroidism (PHPT), pituitary adenoma (PA), and pancreatic neuroendocrine tumors (pNET).
• The predictive value of MEN1 gene mutations for clinical presentation in affected individuals remains debated.

Purpose of the Study:

• To investigate the relationship between MEN1 gene mutations and clinical manifestations in MEN1 patients.
• To identify novel mutations within the MEN1 gene.

Main Methods:

• Retrospective, single-center study involving clinical and genetic analysis of 90 MEN1 patients.
• Identification of MEN1 mutations through genetic analysis.

Main Results:

• MEN1 mutations were identified in 74.4% of patients (67/90) across 31 families.
• Twenty-nine distinct heterozygous mutations were found, including 6 novel point mutations and one large deletion.
• Truncating MEN1 mutations significantly predicted the development of pNETs (OR=5.8) and PHPT (OR=4.3).

Conclusions:

• The study identified a substantial number of novel mutations in MEN1 patients, corroborating prior findings.
• Truncating mutations in the MEN1 gene are associated with a higher frequency of pNETs and PHPT.