Mutational analysis of the PTH 3'-untranslated region in parathyroid disorders.
Mutational analysis of the PTH 3'-untranslated region in parathyroid disorders.
复制标题
甲状旁腺疾病中 PTH 3-非翻译区的突变分析。
DOI：
10.1111/j.1365-2265.2006.02670.x
复制
发表时间：
2006
影响因子：
3.2
通讯作者：
Arnold,Andrew
中科院分区：
文献类型：
--
作者：
Costa-Guda,Jessica;Lauter,Kelly;Naveh-Many,Tally;Silver,Justin;Arnold,Andrew
基因非翻译区（UTR）序列的改变是人类疾病的重要因素，包括遗传性血栓形成倾向，遗传性高铁蛋白血症-白内障和脆性X智力低下综合征。最近，对编码甲状旁腺激素的PTH基因的3′-UTR的功能研究表明，它是甲状旁腺功能障碍患者致病突变的潜在靶点。PTH基因表达的调节部分通过蛋白质与PTH mRNA 3′-UTR中特异性26个核苷酸不稳定元件的结合以序列依赖性方式发生。因此，PTH 3 ′-UTR已成为甲状旁腺功能障碍的重要潜在贡献者。因此，我们试图严格检查原发性和继发性甲状旁腺疾病患者的PTH 3 ′-UTR，包括原发性甲状旁腺增生、继发性甲状旁腺增生、散发性甲状旁腺腺瘤和遗传基础未知的家族性甲状旁腺功能减退症。对29例继发性甲状旁腺增生患者的42个甲状旁腺和8例遗传基础未知的家族性甲状旁腺功能减退症患者的24名患者的外周血白细胞进行了PTH基因3′-UTR突变检测。尽管在这些形式的甲状旁腺功能障碍中存在可识别的DNA序列改变，但PTH 3 ′-UTR突变不太可能经常参与其发病机制。
ObjectiveSequence alterations in untranslated regions (UTRs) of genes are important contributors to human diseases, including hereditary thrombophilia, hereditary hyperferritinaemia‐cataract and fragile X mental retardation syndromes. Recently, functional studies of the 3′‐UTR of thePTHgene, encoding parathyroid hormone, have highlighted it as a potential target for pathogenic mutations in patients with parathyroid dysfunction. Regulation ofPTHgene expression occurs in part through protein binding to a specific 26 nucleotide instability element in the 3′‐UTR of PTH mRNA, in a sequence‐dependent manner. Thus, thePTH3′‐UTR has emerged as an important potential contributor to parathyroid dysfunction. Therefore, we sought to rigorously examine thePTH3′‐UTR in patients with primary and secondary parathyroid disorders, including primary parathyroid hyperplasia, secondary parathyroid hyperplasia, sporadic parathyroid adenoma and familial hypoparathyroidism of unknown genetic basis.Patients and designTwenty‐one parathyroid glands from 14 patients with primary parathyroid hyperplasia, 40 sporadic parathyroid adenomas from 40 patients, 42 parathyroid glands from 29 patients with secondary parathyroid hyperplasia and peripheral blood leucocytes from 24 affected members of eight kindreds with familial hypoparathyroidism of unknown genetic basis were examined for mutations in the 3′‐UTR of thePTHgene.ResultsNo alterations from the normal sequence were detected in any of the 127 samples examined.ConclusionsBased on the absence of identifiable DNA sequence alterations in these forms of parathyroid dysfunction, it is unlikely that mutation of thePTH3′‐UTR contributes frequently to their pathogenesis.