Kim Boram, Lee Seung Hun, Ahn Chang Ho, Jang Han Na, Cho Sung Im, Lee Jee-Soo, Lee Yu-Mi, Kim Su-Jin, Sung Tae-Yon, Lee Kyu Eun, Lee Woochang, Koh Jung-Min, Seong Moon-Woo, Kim Jung Hee
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Endocrinol Metab (Seoul). 2024 Dec;39(6):956-964. doi: 10.3803/EnM.2024.2008. Epub 2024 Nov 18.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants.
This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines.
A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040).
The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.
多发性内分泌腺瘤1型（MEN1）是一种常染色体显性疾病，其特征为多个内分泌器官发生肿瘤，由MEN1基因变异引起。本研究分析了韩国队列中MEN1的临床和遗传特征，确定了常见表现和遗传变异，包括新的变异。
这项多中心回顾性研究回顾了2012年1月至2022年9月期间在韩国三个三级中心接受治疗的117例MEN1患者的病历。收集了患者的人口统计学信息、肿瘤表现、结局以及MEN1基因检测结果。变异按照美国医学遗传学与基因组学学会（ACMG）和法国神经内分泌肿瘤肿瘤遗传学网络（TENGEN）指南进行分类。
共纳入117例患者，包括55例家族性病例，诊断时的平均年龄为37.4±15.3岁。原发性甲状旁腺功能亢进被确定为最常见的表现（84.6%）。胃肠胰神经内分泌肿瘤和垂体神经内分泌肿瘤（PitNET）的患病率分别为77.8%（n = 91）和56.4%（n = 66）。基因检测在101例患者中发现了61种不同的MEN1变异，其中18种为新变异。根据TENGEN指南对4种变异进行了重新分类。与非截短变异患者（n = 25）相比，截短变异患者（n = 72）的PitNET患病率更高（59.7%对36.0%，P = 0.040）。
MEN1中截短变异与PitNET患病率增加之间的关联强调了基因特征在指导该疾病临床管理中的重要性。我们的研究揭示了韩国人群中MEN1的临床和遗传特征。
