Flanagan D E, Armitage M, Clein G P, Thakker R V
Department of Endocrinology, Royal Bournemouth Hospital, UK.
Clin Endocrinol (Oxf). 1996 Jul;45(1):117-20.
Multiple endocrine neoplasia type one (MEN 1) is characterized by tumours of the parathyroid glands, pancreatic islet cells and the anterior pituitary and follows an autosomal dominant pattern of inheritance. We report identical twins born to a family known to have the MEN 1 syndrome. The twins were identical until puberty. The first twin underwent puberty normally; the second, however, suffered an early pubertal arrest and was subsequently found to have a prolactinoma. Both were also subsequently shown to have primary hyperparathyroidism. Genetic studies have since confirmed the twins identical for the affected haplotype and show that this is inherited from the father who also has MEN 1. The gene for MEN 1 has now been localized to the long arm of chromosome 11. The current hypothesis is that expression of the syndrome involves two separate genetic mutations. The first mutation is inherited and thus present in all cells but the tumour manifests itself in the endocrine tissue only after a second mutation that represents elimination of the normal allele. In the case described the twins are proven genetically identical. The marked phenotypic difference between the two must, by inference, represent a second somatic mutation and is further supportive evidence of the two-mutation model of tumour expression.
多发性内分泌腺瘤病1型（MEN 1）的特征是甲状旁腺、胰岛细胞和垂体前叶发生肿瘤，呈常染色体显性遗传模式。我们报告了一对双胞胎，他们出生于一个已知患有MEN 1综合征的家庭。这对双胞胎在青春期前长得一模一样。第一个双胞胎正常进入青春期；然而，第二个双胞胎青春期过早停滞，随后被发现患有催乳素瘤。两人随后还被发现患有原发性甲状旁腺功能亢进症。此后的基因研究证实这对双胞胎的受影响单倍型相同，并表明这是从同样患有MEN 1的父亲那里遗传来的。MEN 1基因现已定位到11号染色体长臂。目前的假说是，该综合征的表达涉及两个独立的基因突变。第一个突变是遗传的，因此存在于所有细胞中，但肿瘤仅在代表正常等位基因缺失的第二个突变后才在内分泌组织中表现出来。在所描述的病例中，这对双胞胎经基因检测被证实完全相同。由此推断，两人之间明显的表型差异一定代表了第二个体细胞突变，这进一步支持了肿瘤表达的双突变模型。
