Objective Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder associated with mutations of the MEN1 gene. MEN1 may present as a familial or a sporadic disorder, with multiple endocrine tumours including parathyroid adenomas or hyperplasias, and pancreatic endocrine and pituitary gland tumours. The aim of this study was to examine the prevalence and spectrum of MEN1 gene mutations in Hungarian patients with familial and sporadic MEN1 and in those with a MEN1-related state.Design Mutation analysis, using temporal temperature gradient gel electrophoresis and direct sequencing of all coding exons and the corresponding exon-intron boundaries of the MEN1 gene, was performed.Patients and measurements Peripheral blood DNA was obtained from 32 patients (19 index patients with familial or sporadic MEN1 and 13 index patients with familial or sporadic MEN1-related state). First degree relatives were also studied.Results Ten different MEN1 gene mutations were identified in 10 index patients, including four novel mutations (A91V, G28A and E26X all in exon 2, and L301R in exon 6). All but one mutation occurred in index patients with familial or sporadic MEN1; the prevalence of mutation was considerably higher in index patients with familial MEN1 (6/6 patients, 100%) than in those with sporadic MEN1 (3/13 patients, 23%). Of the 13 index patients with a MEN1-related state, only one patient with recurrent isolated primary hyperparathyroidism had a MEN1 gene mutation. Family screening indicated mutations in six symptomatic and in one asymptomatic first degree relative.Conclusion These results confirm previous reports on the high prevalence of novel MEN1 gene mutations among patients with MEN1, and support the questionable efficacy of mutation screening in patients with sporadic MEN1-related states.

The genotype and phenotype characteristics of Hungarian patients with RET proto-oncogene mutations operated on for hereditary medullary thyroid cancer (MTC) were studied. The genetic screening was performed in two centers and 40 patients with hereditary MTC or C-cell hyperplasia (CCH) from 18 unrelated families were analyzed. One patient having a mutation in exon 16 (Met918Thr) presented with the MEN2B phenotype, six patients from two families had hereditary MTC without pheochromocytoma (pheo) and primary hyperparathyroidism (PHPT), whereas 33 patients from 15 families showed the MEN2A phenotype. Two different mutations were identified in exon 10 (Cys609Tyr and Cys609Ser), five different mutations were present in exon 11 (Cys634Phe, Cys634Arg, Cys634Tyr, Cys634Trp and Cys634Ser), and two different mutations were localized in exon 14 (Val804Met and Val804Leu). Mutations in exon 10 were associated with hereditary MTC (Cys609Tyr) or with MEN2A syndrome (Cys609Ser). Mutations in exon 11 were always associated with the MEN2A phenotype. PHPT was present in one patient with mutation in exon 14 (Val804Met), whereas all other patients affected with mutations in exon 14 had hereditary MTC without PHPT and/or pheos.