Parathyroid MEN1 gene mutations in relation to clinical characteristics of nonfamilial primary hyperparathyroidism
Parathyroid MEN1 gene mutations in relation to clinical characteristics of nonfamilial primary hyperparathyroidism
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DOI：
10.1210/jc.83.8.2960
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发表时间：
1998-08-01
影响因子：
5.8
通讯作者：
Åkerström, G
中科院分区：
文献类型：
--
作者：
Carling, T;Correa, P;Åkerström, G
原发性甲状旁腺功能亢进症（pHPT）的生化体征和症状的严重程度在不同的患者之间是不同的，并且对非家族性pHPT的临床特征与甲状旁腺肿瘤的遗传异常之间的任何耦合知之甚少。最近在非家族性pHPT的甲状旁腺肿瘤中发现了染色体11q13处MEN1基因的突变。应用微卫星分析11q13杂合性缺失（洛）和编码外显子的DNA测序，研究了49例具有不同症状、手术结果、组织病理学诊断和非家族性pHPT生化体征的甲状旁腺病变患者的MEN 1基因。在13个肿瘤中检测到11q13的等位基因丢失，其中6个表现出先前未被识别的MEN1基因的体细胞错义和移码缺失突变。许多检测到的突变很可能导致无功能的menin蛋白，与肿瘤抑制机制一致。HPT的临床和生化特征与洛缺失和MEN1基因突变无关。然而，在轻度高钙血症和正常血清PTH水平的患者的小甲状旁腺腺瘤中，11 q13的洛缺失和MEN1基因突变的证明表明MEN1基因功能的改变对于轻度散发性pHPT的发生也可能是重要的。
Biochemical signs and severity of symptoms of primary hyperparathyroidism (pHPT) differ among patients, and little is known of any coupling of clinical characteristics of nonfamilial pHPT to genetic abnormalities in the parathyroid tumors. Mutations in the recently identified MEN1 gene at chromosome 11q13 have been found in parathyroid tumors of nonfamilial pHPT. Using microsatellite analysis for loss of heterozygosity (LOH) at 11q13 and DNA sequencing of coding exons, the MEN1 gene was studied in 49 parathyroid lesions of patients with divergent symptoms, operative findings, histopathological diagnosis, and biochemical signs of nonfamilial pHPT. Allelic loss at 11q13 was detected in 13 tumors, and 6 of them demonstrated previously unrecognized somatic missense and frameshift deletion mutations of the MEN1 gene. Many of the detected mutations would most likely result in a nonfunctional menin protein, consistent with a tumor suppressor mechanism. Clinical and biochemical characteristics of HPT were apparently unrelated to the presence or absence of LOH and the MEN1 gene mutations. However, the demonstration of LOH at 11q13 and MEN1 gene mutations in small parathyroid adenomas of patients with slight hypercalcemia and normal serum PTH levels suggest that altered MEN1 gene function may also be important for the development of mild sporadic pHPT.