Introduction: Multiple endocrine neoplasia type 1 (MEN 1) may present as a familial or a sporadic disorder with multiple endocrine tumours including parathyroid adenomas or hyperplasias, tumours of endocrine pancreatic and pituitary gland. Familial and sporadic MEN 1-related states which do not fulfill current diagnostic criteria but may be related to MEN 1 syndrome have been also described.
Aims: The aim of this study was to examine the prevalence and spectrum of MEN1 gene mutations in Hungarian patients with familial and sporadic MEN 1 and in those with an MEN 1-related state.
Methods: We performed mutation analysis using temporal temperature gradient gel electrophoresis (TGGE) and direct sequencing of the entire coding and exon-intron boundaries of the MEN1 gene. Genomic DNA was obtained from 32 patients (19 index patients with familial or sporadic MEN 1 and 13 index patients with familial or sporadic MEN 1-related state). Family screening was performed in families of patients with identified MEN1 mutation.
Results: Ten different MEN 1 gene mutations were identified in 10 index patients, including 5 novel mutations (A91V, G28A and E26X in exon 2, L301R in exon 6, and C354X in exon 8). All but one mutations occurred in index patients with familial or sporadic MEN 1; the prevalence of mutation was considerably higher in index patients with familial MEN 1 (6/6 patients, 100%) than in those with sporadic MEN 1 (3/13 patients, 23%). Of the 13 index patients with MEN 1-related state, only one patient with recurrent isolated primary hyperparathyroidism had MEN1 gene mutation. Family screening indicated mutations in 6 symptomatic and in one asymptomatic first-degree relative.
Conclusions: These results confirm previous reports on the high prevalence of novel MEN1 gene mutations among patient with MEN 1, and support the questionable efficacy of mutation screening in patients with sporadic MEN 1-related states.