MEN1 c.825-1G>A mutation in a family with multiple endocrine neoplasia type 1: A case report
MEN1 c.825-1G>A mutation in a family with multiple endocrine neoplasia type 1: A case report
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DOI：
10.3892/mmr.2015.4138
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发表时间：
2015-10-01
影响因子：
3.4
通讯作者：
Xu, Yuan
中科院分区：
文献类型：
--
作者：
Ning, Zhiwei;Wang, Ou;Xu, Yuan
多发性内分泌瘤1型（MEN 1）是一种常染色体显性遗传疾病，其特征是在包括甲状旁腺、胃肠道内分泌组织和垂体前叶在内的组织中同时发生肿瘤和增生。肿瘤抑制基因MEN的杂合性生殖系突变是该疾病的原因。由于该病相对罕见，文献中很少报告MEN 1患者的治疗和长期随访;因此，对肿瘤生物学和行为的了解有限，临床表现异质。本病例报告观察到一个MEN 1 c.825-1G>A突变的家族。临床特征和治疗随访>20年。对该家系进行详细的家族史调查和随访。通过标准方法从外周白细胞提取基因组DNA。测定了白细胞DNA MEN基因的编码序列，包括9个编码外显子和16个剪接点。先证者表现为胃泌素瘤、垂体瘤、甲状旁腺功能亢进、胸腺瘤和肺类癌，随访时间为35 ~ 54岁。在20年期间，患者接受了四次手术：39岁时经蝶窦腺瘤切除术，随后进行术后放疗; 40岁时增生的甲状旁腺切除术; 41岁时切除胰腺、头颈部、十二指肠、胆囊、胆管、胃次全（4/5）和幽门区淋巴结; 49岁时接受了胸腺切除术和左肺类癌切除术。患者死于不相关的创伤，病程相对稳定。DNA序列分析显示该家系存在MEN基因c.825-1G>A或IVS 5-1G>A突变。对该家系中的两名携带者进行了鉴定和随访。数据表明，虽然MEN 1是一种涉及多个器官和系统的复杂疾病，但MEN 1肿瘤应被认为是可手术治愈的。如果患者得到由具有内分泌肿瘤患者诊断和治疗经验的相关专家组成的多学科团队的适当护理，患者可能会有相对积极的预后。
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease characterized by combined occurrence of tumors and hyperplasia in tissues including the parathyroid, gastrointestinal endocrine tissue and anterior pituitary. Heterozygous germline mutation of the tumor suppressor gene MEN] is the cause of the disease. Treatment and long-term follow up of patients with MEN1 are rarely reported in the literature due to the relative rarity of the disease; thus, there is limited understanding of tumor biology and behavior, and heterogeneous clinical presentation. This case report observed a family that presented with MEN1 c.825-1G>A mutation. The clinical features and treatment were followed up for >20 years. Detailed family history of this pedigree was investigated and followed up. Genomic DNA was extracted by standard methods from peripheral leukocytes. The coding sequence, including 9 coding exons and 16 splice junctions of the MEN] gene of leukocyte DNA was determined. The proband presented with gastrinoma, pituitary tumors, hyperparathyroidism, thymoma and lung carcinoid tumors, and was followed from age 35 to 54 years old. During the 20 years, the patient underwent four surgeries: Trans-sphenoidal adenomectomy, followed by post operative radiotherapy at 39 years; hyperplasia parathyroid gland resection at 40 years; removal of pancreatic, head and neck, duodenal, gallbladder, bile duct, subtotal gastric (4/5) and pyloric region lymph nodes at age 41; and a thymectomy and left lung carcinoid tumor removal procedure at the age of 49. The patient died of unrelated trauma and had a relatively stable illness course. DNA sequence analysis revealed MEN] gene c.825-1G>A or IVS 5-1G>A mutation in the family. Two carriers in the pedigree were identified and followed up. Data indicated that although MEN1 is a complex disease involving multiple organs and systems, MEN1 tumors should be considered surgically curable. If patients are properly cared for by multidisciplinary teams comprising of relevant specialists with experience in the diagnosis and treatment of patients with endocrine tumors, patients may have a relatively positive prognosis.