NOVEL LIKELY PATHOGENIC MEN1 MOSAIC MUTATION IN THE FAMILY WITH MEN-1 SYNDROME

Introduction:Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal dominant syndrome caused by inactivating mutations in the MEN1 tumor suppressor gene and characterized by polyglandular pathology. More than 1600 MEN1 mutations have been reported. Conventional genetic testing is positive in 70-90% of patients with the typical phenotype, but negative in approximately 10-30% of families with MEN-1. Advanced genetic techniques can help detect rare cases of MEN1 mosaicism.Methods:We performed several genetic studies of MEN-1 family members with a clinical phenotype of disease, including primary hyperparathyroidism (PHPT), multiple pancreatic neuroendocrine tumors (NETs), and a pituitary microadenoma. This allowed us to detect a new likely pathogenic mosaic mutation in the MEN1 gene. DNA isolated from peripheral blood and parathyroid tissue was sequenced by Sanger, Next Generation Sequencing (NGS) and Oxford Nanopore long-read sequencing (ONT sequencing).Results:A novel likely pathogenic (according to ACMG-AMP guidelines) MEN1 mosaic mutation was confirmed by ONT sequencing, but not by Sanger or NGS.