Novel mutations in Serbian MEN1 patients: Genotype-phenotype correlation

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer syndrome characterized by the occurrence of primary hyperparathyroidism (PHPT), pituitary adenoma (PA) and pancreatic neuroendocrine tumor (pNET). Whether the underlying mutations in M EN1 gene predict clinical presentation of affected heterozygotes or not, is still a matter of a debate. Methods: Clinical and genetic analysis of 90 consecutive MEN1 patients was performed in a retrospective, single - center study. Results: M EN1 mutation was found in 67 (74.4% ) patients belonging to 31 different families. Twenty nine different heteozygous mutations were found, including 6 novel point mutations (W 220G , 941delG, 1088del7, 1184insA, 1473del10, 1602del17) and one large deletion of exon 8. Truncating mutations predicted development of pNETs (O R = 5.8, 95% CI 1.7 - 19.7%) and PHPT (O R = 4.3, 95% CI 1.5 - 12.4%). Conclusions: Large number of novel mutations among MEN1 patients confirmed previously reported data. PNETs and PHPT were more frequent in patients with truncating mutations.