MEN1 c.825­1G>A mutation in a family with multiple endocrine neoplasia type 1: A case report.

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 MEN1 is the cause of the disease. Treatment and long­term 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.825­1G>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 MEN1 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: Trans­sphenoidal 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 MEN1 gene c.825­1G>A or IVS 5­1G>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.