Abstract
BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disorder characterized by the occurrence of combined tumors in different glands, usually the parathyroid, pancreas and pituitary, as well as in other parts of the digestive tract. The present study describes the phenotype of a Brazilian family with MEN1 caused by a previously unreported MEN1 gene mutation. CASE REPORT: We report the case of a 41-year-old male, the proband, who presented with angiofibromas, primary hyperparathyroidism, macroprolactinoma, and pancreatic neuroendocrine tumor. Next generation sequencing analysis of the MEN1 gene in the patient's peripheral blood DNA sample revealed a deletion of 16 base pairs (c.1366-12_1369del;p) resulting in a framing error. Additional 5 members of the family (4 brothers and a first cousin) presented with clinical features of MEN1. All brothers underwent mutation screening and tested positive for the same genetic variant. Two of them were also diagnosed with papillary thyroid carcinoma. DISCUSSION: The c.1366-12_1369del;p mutation is located between the 10th and last exon of the MEN 1 gene and it's preceding intron, encompassing the canonical sites in the splice junction. The 10th exon of MEN1, possibly lost with this variant, encodes the last 163 amino acids that compose the Menin protein's C-terminal region, which harbors nuclear localization signals essential for its internalization into the nuclear compartment and interaction with the nuclear matrix. CONCLUSION: Our case reports add to the literature the description of a new pathogenic variant of the MEN 1 gene.