Clinical Profile and Mutations Associated with Multiple Endocrine Neoplasia-Type1 (MEN1) and Their First-Degree...

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Multiple Endocrine Neoplasia type-1 (MEN1) is an inherited disorder characterized by tumors in parathyroid, pancreatic islet, and pituitary glands.
• MEN1 gene mutations are found in approximately 90% of patients, but the mutation spectrum in India requires further definition.

Purpose of the Study:

• To characterize the clinical presentation and genetic basis of MEN1 in an Indian cohort.
• To investigate mutations in the MEN1 gene and related genes (CDKN1B, CaSR) in suspected MEN1 cases.

Main Methods:

• Prospective enrollment of 40 clinically suspected MEN1 cases over six years.
• Clinical data collation, including tumor types and treatment.
• Comprehensive mutational analysis of the MEN1 gene, its UTRs, CDKN1B, and CaSR genes.

Main Results:

• Of 32 definite MEN1 patients, all had hyperparathyroidism, 68.7% had neuroendocrine tumors, and 66% had pituitary adenomas.
• MEN1 mutations were identified in 56.5% of index cases and 55.5% of affected relatives.
• A significant proportion of MEN1 mutation-negative cases harbored the CDKN1B p.V109G polymorphism, and MEN1-like cases showed no mutations in screened genes.

Conclusions:

• This study provides insights into MEN1 mutation patterns in India.
• The high rate of MEN1 mutation-negative cases and the presence of CDKN1B polymorphism suggest potential alternative genetic factors in MEN1 pathogenesis.