Familial Multiple Endocrine Neoplasia Type I: A New Look at Pathophysiology

Brandi, Maria Luisa; Marx, Stephen J.; Aurbach, G. D.; Fitzpatrick, L.A.

doi:10.1210/edrv-8-4-391

Cited by 173 publications

(98 citation statements)

References 99 publications

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“…The clinical manifestation of MEN-1 is characterized by pituitary and parathyroid hyperplasias and adenomas, neuroendocrine tumors of the gut, and carcinoids of the lung (1); the disease occurs either sporadically or as a familial trait with an autosomal dominant mode of inheritance (2). Germ line mutations in the MEN1 gene have been described in familial and sporadic MEN-1 patients (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of the Menin Tumor Suppressor Protein on Serine 543 and Serine 583

MacConaill

Hughes

Rozenblatt-Rosen

et al. 2006

Molecular Cancer Research

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Section: Introductionmentioning

confidence: 99%

Phosphorylation of the Menin Tumor Suppressor Protein on Serine 543 and Serine 583

MacConaill

Hughes

Rozenblatt-Rosen

et al. 2006

Molecular Cancer Research

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“…To a lesser extent, other endocrine and non-endocrine tissues can be affected: carcinoids, lipomas, pinealomas, adrenocortical and thyroid follicular tumors and spinal cord ependymomas are also associated with MEN 1 (1,2).…”

Section: Introductionmentioning

confidence: 99%

MEN1 gene mutation analysis in Italian patients with multiple endocrine neoplasia type 1

Morelli

Falchetti

Martineti

et al. 2000

European Journal of Endocrinology

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Multiple endocrine neoplasia type 1 (MEN 1) is a familial syndrome characterized by parathyroid, enteropancreatic and pituitary tumors. The gene responsible for this syndrome is localized at chromosomal 11q13 region and DNA markers from this region cosegregate with the disease. The recent identification of the MEN1 gene, encoding for a protein termed menin of 610 amino acids, allowed mutational screening to be performed both in affected families and sporadic cases. To date many different heterozygous mutations, spreading across all the encoding sequence, have been identified in MEN 1 patients with no apparent mutational hot spots or genotype-phenotype correlation. To analyze the genetic alterations of the MEN1 gene occurring in Italian patients we performed mutational screening by Denaturant Gradient Gel Electrophoresis followed by sequencing of exons 2-10 of the MEN1 gene in 27 Italian MEN 1 families and in five sporadic cases. We identified 17 different heterozygous mutations in 60% of analyzed cases. Twelve of these mutations are novel. Two mutations each occurred twice in unrelated families but no evidence of genotype-phenotype correlation can be established for these families. The extension of genetic diagnosis to asymptomatic family members allowed the identification of 10 MEN1 mutant gene carriers, one newly described and nine previously detected by linkage analysis with DNA markers from the 11q13 region. Our findings add new information to the diversity of mutations occurring in the MEN1 gene and confirm that the mutational screening of MEN 1 is a useful approach to detect individuals at higher risk of developing MEN 1-associated tumors.

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“…Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited disorder with a high degree of penetrance and some variability of expression (1). Affected individuals typically have tumors of the parathyroid gland, endocrine pancreas and anterior pituitary.…”

Section: Introductionmentioning

confidence: 99%

A novel mutation of the MEN1 gene in a Japanese kindred with familial isolated primary hyperparathyroidism

Honda

Tsukada²,

Tanaka³

et al. 2000

European Journal of Endocrinology

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Objective: To determine whether familial isolated hyperparathyroidism (FIHP) is a variant of multiple endocrine neoplasia type 1 (MEN1) we analyzed the MEN1 gene in such a kindred. Design and methods:The study included the 70-year-old proband and nine relatives. Blood was drawn for biochemical evaluation and germline mutation analysis by direct sequencing of the MEN1 gene amplified by PCR. A hyperplastic parathyroid gland obtained from a family member served for a loss of heterozygosity (LOH) study. Results: Three members from two generations in this kindred were found to have primary hyperparathyroidism, while none had clinical or biochemical evidence of MEN1, MEN2 or hyperparathyroidismjaw tumor syndrome. Analysis of germline DNA in the proband showed a missense mutation (GGC → GAC) at codon 305 in exon 7 of the MEN1 gene that predicts an amino acid change from glycine to aspartic acid (G305D). This mutation segregated with primary hyperparathyroidism in the kindred, and, in addition, there were two asymptomatic mutant-gene carriers at relatively advanced ages. In contrast, the mutation was not detected in genomic DNA from five unaffected individuals and from 50 healthy subjects. The LOH study showed a loss of the wild-type allele, which confirmed that a functional defect of the MEN1 gene product, menin, is etiological for FIHP. Conclusions: FIHP is a genetically heterogeneous disease with a subset linked to MEN1, most likely representing a variant of MEN1. The late onset and the reduced penetrance of disease found in this kindred may be related to the site and the type of mutation, although the precise mechanism involved is unknown at present.

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Familial Multiple Endocrine Neoplasia Type I: A New Look at Pathophysiology

Cited by 173 publications

References 99 publications

Phosphorylation of the Menin Tumor Suppressor Protein on Serine 543 and Serine 583

Phosphorylation of the Menin Tumor Suppressor Protein on Serine 543 and Serine 583

MEN1 gene mutation analysis in Italian patients with multiple endocrine neoplasia type 1

A novel mutation of the MEN1 gene in a Japanese kindred with familial isolated primary hyperparathyroidism

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