MEN1 gene mutations in Hungarian patients with multiple endocrine neoplasia type 1

Katalin Balogh, L. Hunyady, A. Patócs, Peter Gergics, Zsuzsa Valkusz, Miklos Toth, K. Rácz

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Abstract

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.

Original languageEnglish
Pages (from-to)727-734
Number of pages8
JournalClinical Endocrinology
Volume67
Issue number5
DOIs
Publication statusPublished - Nov 2007

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Multiple Endocrine Neoplasia Type 1
Mutation
Genes
Exons
Endocrine Glands
Parathyroid Neoplasms
Denaturing Gradient Gel Electrophoresis

ASJC Scopus subject areas

  • Endocrinology

Cite this

MEN1 gene mutations in Hungarian patients with multiple endocrine neoplasia type 1. / Balogh, Katalin; Hunyady, L.; Patócs, A.; Gergics, Peter; Valkusz, Zsuzsa; Toth, Miklos; Rácz, K.

In: Clinical Endocrinology, Vol. 67, No. 5, 11.2007, p. 727-734.

Research output: Contribution to journalArticle

Balogh, Katalin ; Hunyady, L. ; Patócs, A. ; Gergics, Peter ; Valkusz, Zsuzsa ; Toth, Miklos ; Rácz, K. / MEN1 gene mutations in Hungarian patients with multiple endocrine neoplasia type 1. In: Clinical Endocrinology. 2007 ; Vol. 67, No. 5. pp. 727-734.
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abstract = "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.",
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N2 - 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.

AB - 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.

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