Multiple endocrine neoplasia type 1 (MEN1)
Multiple endocrine neoplasia type 1 (MEN1)
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DOI：
10.1016/j.beem.2010.07.003
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发表时间：
2010-06-01
影响因子：
7.4
通讯作者：
Thakker, Rajesh V.
中科院分区：
文献类型：
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作者：
Thakker, Rajesh V.
多发性内分泌瘤1型（MEN 1）是一种常染色体显性遗传疾病，其特征是发生甲状旁腺、胰腺和垂体前叶肿瘤。男人！Menin基因由10个外显子组成，编码610个氨基酸的蛋白质，称为Menin。Menin主要是一种核蛋白，在转录调控、基因组稳定性、细胞分裂和增殖中发挥作用。生殖系突变通常导致MEN 1或偶尔导致称为家族性孤立性甲状旁腺功能亢进症（FIHP）的等位基因变异。MEN 1肿瘤通常具有MEN 1基因座的杂合性缺失（洛），这与MEN 1的肿瘤抑制作用一致。此外，在MEN 1和非MEN 1内分泌肿瘤中也报告了MEN 1的体细胞异常。迄今为止，已报告了超过1300种突变，预计其中大多数（>70%）会导致Menin的截短形式。突变分散在MEN 1基因的>9 kb基因组序列中。其中c.249_252delGTCT（密码子83-84处缺失）、c.1546_1547insC（密码子516处插入）、c.1378C>T（Arg 460 Ter）和c.628_631delACAG（密码子210-211处缺失）四种基因型分别占4.5%、2.7%、2.6%和2.5%。然而，与相同突变的患者及其家族的临床特征的比较揭示了表型-基因型相关性的缺乏。大多数MEN 1突变可能会破坏Menin与其他蛋白质的相互作用，从而改变细胞周期调控和增殖中的关键事件。(C)2010爱思唯尔有限公司保留所有权利。
Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal-dominant disorder characterised by the occurrence of tumours of the parathyroids, pancreas and anterior pituitary. The MEN! gene, consists of 10 exons that encode a 610-amino acid protein referred to as Menin. Menin is predominantly a nuclear protein that has roles in transcriptional regulation, genome stability, cell division and proliferation. Germ-line mutations usually result in MEN1 or occasionally in an allelic variant referred to as Familial Isolated Hyperparathyroidism (FIHP). MEN1 tumours frequently have loss of heterozygosity (LOH) of the MEN1 locus, which is consistent with a tumour suppressor role of MEN1. Furthermore, somatic abnormalities of MEN1 have been reported in MEN1 and non-MEN1 endocrine tumours. To date, over 1300 mutations have been reported, and the majority (>70%) of these are predicted to lead to truncated forms of Menin. The mutations are scattered throughout the >9 kb genomic sequence of the MEN1 gene. Four, which consist of c.249_252delGTCT (deletion at codons 83-84), c.1546_1547insC (insertion at codon 516), c.1378C>T (Arg460Ter) and c.628_631delACAG (deletion at codons 210-211) have been reported to occur frequently in 4.5%, 2.7%, 2.6% and 2.5% of families, respectively. However, a comparison of the clinical features in patients and their families with the same mutations reveals an absence of phenotype-genotype correlations. The majority of MEN1 mutations are likely to disrupt the interactions of Menin with other proteins and thereby alter critical events in cell cycle regulation and proliferation. (C) 2010 Elsevier Ltd. All rights reserved.