Clerici T, Schmid C, Komminoth P, Lange J, Spinas G A, Brändle M
Department of Surgery, Kantonsspital St. Gallen, Switzerland.
Swiss Med Wkly. 2001 Jun 30;131(25-26):381-6. doi: 10.4414/smw.2001.09730.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease characterised by the combined occurrence of tumours of the parathyroid glands, the enteropancreatic neuroendocrine system and the anterior pituitary gland. The genetic defect has been mapped to the long arm of chromosome 11q13, and the MEN1-gene was recently identified by positional cloning. Genetic screening for MEN1 germline mutations allows the identification of gene carriers in affected kindreds. Biochemical and radiological screening for MEN1 tumours allows an earlier diagnosis and treatment, and, thus may reduce morbidity and mortality. Since there is no consensus about the frequency and the extent of the necessary screening investigations, evaluation of proposed screening programs is of importance.
The aims of our study were to identify the MEN1-gene mutations and to detect the gene-carriers in 10 Swiss MEN1 families, as well as to assess biochemical and radiological screening methods. The study included 45 members from 10 MEN1 families.
Every family had a different type of MEN1-gene mutation. Thirty out of 45 family members were gene mutation carriers. Twenty-two MEN1-gene carriers had typical MEN1 tumours: parathyroid, enteropancreatic and pituitary tumours were found in 21, 14 and 1 patients, respectively. Applying a defined screening program the following manifestations in asymptomatic MEN1-gene carriers were detected: 9 primary hyperparathyroidism, 3 nonfunctioning pancreatic tumours, 1 gastrinoma, 1 nonfunctioning microadenoma of the pituitary and 1 macronodular adrenal hyperplasia.
The genetic screening facilitates the identification of individuals who carry MEN1-gene mutations, and allows one to exclude non-mutant gene carriers from further investigations. The prospective biochemical and radiological screening of gene mutation carriers allows the earlier detection of MEN1-associated tumours. Therefore, it might be expected that morbidity and mortality of the MEN1 could be reduced.
多发性内分泌腺瘤1型（MEN1）是一种常染色体显性疾病，其特征为甲状旁腺、肠胰神经内分泌系统和垂体前叶肿瘤合并出现。基因缺陷已定位到11号染色体长臂11q13，最近通过定位克隆确定了MEN1基因。对MEN1种系突变进行基因筛查可在受影响的家族中识别基因携带者。对MEN1肿瘤进行生化和放射学筛查可实现早期诊断和治疗，从而可能降低发病率和死亡率。由于对于必要筛查检查的频率和范围尚无共识，因此对提议的筛查方案进行评估很重要。
我们研究的目的是在10个瑞士MEN1家族中识别MEN1基因突变并检测基因携带者，同时评估生化和放射学筛查方法。该研究包括来自10个MEN1家族的45名成员。
每个家族都有不同类型的MEN1基因突变。45名家族成员中有30名是基因突变携带者。22名MEN1基因携带者患有典型的MEN1肿瘤：甲状旁腺、肠胰和垂体肿瘤分别在21例、14例和1例患者中发现。应用特定的筛查方案，在无症状的MEN1基因携带者中检测到以下表现：9例原发性甲状旁腺功能亢进、3例无功能性胰腺肿瘤、1例胃泌素瘤、1例垂体无功能性微腺瘤和1例大结节性肾上腺增生。
基因筛查有助于识别携带MEN1基因突变的个体，并允许将非突变基因携带者排除在进一步检查之外。对基因突变携带者进行前瞻性生化和放射学筛查可早期发现与MEN1相关的肿瘤。因此，预计MEN1的发病率和死亡率可能会降低。
