Department of Gastroenterology, Marmara University School of Medicine, Istanbul, Turkey.
Department of Medical Genetics, Marmara University School of Medicine, Istanbul, Turkey.
Turk J Gastroenterol. 2020 Jul;31(7):508-514. doi: 10.5152/tjg.2020.19830.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized by tumors arising from endocrine glands with no specific genotype-phenotype correlation. Herein, we report the largest Turkish kindred with MEN1 inherited a scarce MEN1 mutation gene.
Sixty-four year-old man, referred to our gastroenterology outpatient clinic for evaluation of pancreatic mass lesion, was diagnosed with MEN1-syndrome after endoscopic ultrasound guided sampling of the mass revealing pancreatic neuroendocrine tumor (pNET), and accompanying primary hyperparathyroidism (PHPT) and pituitary tumor. Genetic analysis by whole gene Sanger sequencing of MEN1 gene identified a frame-shift mutation in exon 10 (c.1680_1683delTGAG). All the relatives of the index case were proposed for clinical and genetic evaluation for MEN1-syndrome.
Of the 25 relatives of the index case, 17 were diagnosed MEN1-syndrome. Eighteen members among all relatives consented to genetic analysis and 11 had the same mutation as the index case. All the mutation positive members had MEN1, while none of mutation negative subjects had any sign of MEN1-syndrome. The frequencies of PHPT, pNET and pituitary tumors in this kindred were 94.1% (16/17), 29.4% (5/17) and 29.4% (5/17) respectively.
We report rare MEN1 gene mutation which was descibed in a single sporadic patient before. It inherited in at least three generations of a large family, which has proven strong dominant effect on MEN1 phenotype. Further researches may be conducted to clarify potential candidacy of this mutation, as a hotspot for MEN1 patients, especially in Turkish population.
多发性内分泌腺瘤病 1 型（MEN1）是一种常染色体显性遗传综合征，其特征为内分泌腺体肿瘤的发生，且无特定的基因型-表型相关性。在此，我们报告了一个最大的土耳其家系，该家系遗传了一种罕见的 MEN1 突变基因。
一位 64 岁男性因胰腺肿块就诊于我们的消化内科门诊，经内镜超声引导下肿块取样发现胰腺神经内分泌肿瘤（pNET），并伴有原发性甲状旁腺功能亢进症（PHPT）和垂体瘤，诊断为 MEN1 综合征。对 MEN1 基因进行全基因 Sanger 测序的基因分析发现外显子 10 中的框移突变（c.1680_1683delTGAG）。对指数病例的所有亲属均提出进行临床和遗传评估 MEN1 综合征。
在指数病例的 25 位亲属中，有 17 位被诊断为 MEN1 综合征。在所有亲属中，有 18 位成员同意进行基因分析，其中 11 位与指数病例有相同的突变。所有突变阳性的成员均患有 MEN1，而无突变的成员均无 MEN1 综合征的任何迹象。该家系中 PHPT、pNET 和垂体瘤的发生率分别为 94.1%（16/17）、29.4%（5/17）和 29.4%（5/17）。
我们报告了一种罕见的 MEN1 基因突变，此前在单个散发性患者中描述过。它在一个大家庭的至少三代中遗传，对 MEN1 表型具有很强的显性效应。进一步的研究可能会进行，以阐明该突变作为 MEN1 患者，特别是土耳其人群的热点的潜在候选性。
