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 MEN1 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: MEN1 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 (W220G, 941delG, 1088del7, 1184insA, 1473del10, 1602del17) and one large deletion of exon 8. Truncating mutations predicted development of pNETs (OR=5.8, 95% CI 1.7 - 19.7%) and PHPT (OR=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.
Uvod: Multipla endokrina neoplazija tip 1 (MEN1) predstavlja autozomalno dominantni kancerski sindrom koji se karakte riše pojavom primarnog hiperparatireoidizma (PHPT), tumora hipofize i pankreasnih neuroendokrinih tumora (pNET). U kojoj meri postojanje heterozigotne mutacije u MEN1 genu određuje kliničku sliku nosilaca i dalje predstavlja predmet diskusije.
Metode: U okviru retrospektivne studije jednog centra, spro vedeno je kliničko i gensko ispitivanje 90 uzastopnih pacijenata sa MEN1 sindromom.
Rezultati: Mutacija u MEN1 genu nađena je kod 67 (74,4%) pacijenata koji su pripadali 31 različitoj porodici. Identifikovano je dvadeset devet različitih heterozigotnih mutacija, uključujući i 6 novootkrivenih (W220G, 941delG, 1088del7, 1184insA, 1473del10, 1602del17) i jednu veli ku deleciju 8. egzona. Mutacije koje dovode do skraćenja proteina predvidele su pojavu pNET (OR=5,8, 95% CI 1,7 – 19,7%) i PHPT (OR=4,3, 95% CI 1,5 – 12,4%).
Zaključak: Veliki broj novootkrivenih mutacija među MEN1 pacijentima je u skladu sa prethodno objavljenim podacima. Pankreasni NET i PHPT su bili značajno češći kod pacijenata sa mutacijama koje dovode do skraćenja proteina.
Keywords: MEN1; genotype; novel mutations; phenotype.