Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states
Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states
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DOI：
10.1093/hmg/6.7.1169
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发表时间：
1997-07-01
影响因子：
3.5
通讯作者：
Marx, SJ
中科院分区：
文献类型：
--
作者：
Agarwal, SK;Kester, MB;Marx, SJ
家族性多发性内分泌肿瘤1型（Familial multiple endocrine neoplasia type 1, FMEN1）是一种常染色体显性性状，以甲状旁腺、胃肠道内分泌组织、垂体前叶等组织的肿瘤为特征，我们最近克隆了MEN1基因，并通过FMEN1突变的发现证实了其身份，我们现在将突变分析扩展到34个不相关的FMEN1先显子，以及散发性MEN1和家族性甲状旁腺功能亢进两种相关状态。散发性MEN1（8/11）和散发性MEN1（47/50）存在较高的杂合性种系MEN1突变，1例散发性MEN1被证实为新的MEN1突变，8个不同的突变在FMEN1基因中被观察到不止一次，40个不同的突变（32个FMEN1和8个散发性MEN1）分布在MEN1基因上，大多数预测MEN1编码蛋白的功能丧失，支持MEN1是肿瘤抑制基因的预测。家族性甲状旁腺功能亢进的5个先证者中未发现MEN1种系突变，提示家族性甲状旁腺功能亢进往往是由其他基因或基因的突变引起的。
Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant trait characterized by tumors of the parathyroids, gastro-intestinal endocrine tissue, anterior pituitary and other tissues, We recently cloned the MEN1 gene and confirmed its identity by finding mutations in FMEN1, We have now extended our mutation analysis to 34 more unrelated FMEN1 probands and to two related states, sporadic MEN1 and familial hyperparathyroidism, There was a high prevalence of heterozygous germline MEN1 mutations in sporadic MEN1 (8/11 cases) and in FMEN1 (47/50 probands), One case of sporadic MEN1 was proven to be a new MEN1 mutation, Eight different mutations were observed more than once in FMEN1, Forty different mutations (32 FMEN1 and eight sporadic MEN1) were distributed across the MEN1 gene, Most predicted loss of function of the encoded menin protein, supporting the prediction that MEN1 is a tumor suppressor gene, No MEN1 germline mutation was found in five probands with familial hyperparathyroidism, suggesting that familial hyperparathyroidism often is caused by mutation in another gene or gene(s).