Servicio de Endocrinología, Metabolismo y Medicina Nuclear, Hospital Italiano de Buenos Aires (HIBA), Buenos Aires, Argentina. E-mail:
Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto Universitario del Hospital Italiano, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Medicina (B Aires). 2024;84(3):433-444.
Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant inherited disease with an estimated prevalence of 2-10:100 000. The main locations of tumors are parathyroid glands (HPT), gastroenteropancreatic tract (GEPT), and anterior pituitary gland (PT). The aim of our investigation was to describe the phenotype and genotype of Argentinian patients with MEN1.
A total of 68 index patients diagnosed with at least two of the three main tumors or one tumor and a relative with MEN1, and 84 first-degree relatives were studied. We sequenced the coding region (exons 2-10); the promoter, exon 1; and the flanking intronic regions of the MEN1 gene, following the Sanger method. We used MLPA in index patients without mutation.
Prevalence of tumors: HPT 87.5%, GEPT 49% (p< 0.001). No statistical differences in the prevalence of HPT vs. PT (68%). Prevalence of pathogenic variants: 90% in familial cases and 51% in sporadic cases. Of the different 36 pathogenic variants, 13 (36.2%) were frameshift micro-rearrangement, 8 (22.2%) were missense, 9 (25%) were nonsense, 3 (8.3%) were mutations in splicing sites, 2 (5.5%) were large deletions and, 1 in-frame micro-rearrangement. We found 7 novel pathogenic variants. Thirty-nine percent (n = 33) of first-degree relatives of 23 families were found to be mutation carriers.
The phenotype and genotype of Argentinian patients was similar to other MEN1 populations. A high frequency of PT and the identification of seven novel mutations are underscored.
多发性内分泌腺瘤病 1 型（MEN1）是一种常染色体显性遗传性疾病，估计患病率为 2-10:100000。肿瘤的主要部位是甲状旁腺（HPT）、胃肠胰神经内分泌肿瘤（GEPT）和垂体前叶（PT）。我们研究的目的是描述阿根廷 MEN1 患者的表型和基因型。
共研究了 68 名至少有三种主要肿瘤中的两种或一种肿瘤和一种 MEN1 相关亲属的索引患者，以及 84 名一级亲属。我们按照 Sanger 法对 MEN1 基因的编码区（外显子 2-10）、启动子、外显子 1 和侧翼内含子区域进行了测序。在没有突变的索引患者中，我们使用 MLPA。
肿瘤患病率：HPT 87.5%，GEPT 49%（p<0.001）。HPT 与 PT 的患病率无统计学差异（68%）。致病性变异的患病率：家族性病例为 90%，散发性病例为 51%。在 36 种不同的致病性变异中，13 种（36.2%）为框移微重排，8 种（22.2%）为错义，9 种（25%）为无义，3 种（8.3%）为剪接位点突变，2 种（5.5%）为大片段缺失，1 种为框内微重排。我们发现了 7 种新的致病性变异。在 23 个家族的 39%（n=33）一级亲属中发现了突变携带者。
阿根廷患者的表型和基因型与其他 MEN1 人群相似。PT 的高发病率和 7 种新突变的鉴定值得关注。
