Multiple Endocrine Neoplasia Type 1 (MEN1) Phenocopy Due to a Cell Cycle Division 73 (CDC73) Variant.
Multiple Endocrine Neoplasia Type 1 (MEN1) Phenocopy Due to a Cell Cycle Division 73 (CDC73) Variant.
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DOI：
10.1210/jendso/bvaa142
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发表时间：
2020-11-01
影响因子：
4.1
通讯作者：
Thakker RV
中科院分区：
文献类型：
--
作者：
Lines KE;Nachtigall LB;Dichtel LE;Cranston T;Boon H;Zhang X;Kooblall KG;Stevenson M;Thakker RV
多发性内分泌肿瘤1型（MEN 1）是一种常染色体显性遗传疾病，其特征是合并发生甲状旁腺肿瘤、垂体腺瘤和胰腺神经内分泌肿瘤（PNEN）。MEN 1是由> 75%的患者的生殖系MEN 1突变引起的，其余25%的患者可能具有未鉴定基因的突变或代表具有基因突变的表型，例如细胞周期分裂73（CDC 73）、钙敏感受体（CASR）和细胞周期蛋白依赖性激酶抑制剂1B（CDKN 1B），其分别与甲状旁腺肌-颌肿瘤综合征、家族性低尿钙高血症1型和MEN 4相关。 在这里，我们报告了一个杂合子c.1138C>T（p.Leu380Phe）CDC 73种系变异在临床诊断的MEN 1患者，根据原发性甲状旁腺功能亢进症，肢端肥大症，和PNEN的组合发生。PNEN的特征证实它是一种神经内分泌肿瘤，因为它对嗜铬粒蛋白和胰高血糖素免疫染色呈阳性。罕见的变异p.Leu380Phe发生在一个高度保守的残基，并使用RNA-Scope进一步分析表明，它与PNEN中CDC 73表达的显着减少有关。以前，已经报道了CDC 73突变与甲状旁腺、肾脏、子宫和外分泌胰腺的肿瘤相关。因此，我们报道了一名患有PNEN和生长激素瘤的患者，该患者具有CDC 73变异，提供了进一步的证据，表明CDC 73变异可能导致MEN 1表型。
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid tumors, pituitary adenomas, and pancreatic neuroendocrine neoplasms (PNENs). MEN1 is caused by germline MEN1 mutations in > 75% of patients, and the remaining 25% of patients may have mutations in unidentified genes or represent phenocopies with mutations in genes such as cell cycle division 73 (CDC73), the calcium sensing receptor (CASR), and cyclin-dependent kinase inhibitor 1B (CDKN1B), which are associated with the hyperparathyroidism-jaw tumor syndrome, familial hypocalciuric hypercalcemia type 1, and MEN4, respectively. Here, we report a heterozygous c.1138C>T (p.Leu380Phe) CDC73 germline variant in a clinically diagnosed MEN1 patient, based on combined occurrence of primary hyperparathyroidism, acromegaly, and a PNEN. Characterization of the PNEN confirmed it was a neuroendocrine neoplasm as it immuno-stained positively for chromogranin and glucagon. The rare variant p.Leu380Phe occurred in a highly conserved residue, and further analysis using RNA-Scope indicated that it was associated with a significant reduction in CDC73 expression in the PNEN. Previously, CDC73 mutations have been reported to be associated with tumors of the parathyroids, kidneys, uterus, and exocrine pancreas. Thus, our report of a patient with PNEN and somatotrophinoma who had a CDC73 variant, provides further evidence that CDC73 variants may result in a MEN1 phenocopy.
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影响因子：
3.8
作者：
Erdas E;Aste N;Pilloni L;Nicolosi A;Licheri S;Cappai A;Mastinu M;Cetani F;Pardi E;Mariotti S;Pomata M
通讯作者：
Pomata M
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通讯作者：
Thakker, RV
影响因子：
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通讯作者：
Thakker RV
影响因子：
4.8
作者：
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通讯作者：
VanDemark, Andrew P.