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NEJM：染色体Xq26微重复和GPR101基因突变导致巨人症和肢端肥大症

2015-01-04 angletears 译 MedSci原创

巨人症肢端肥大症生长激素基因突变
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巨人症及肢端肥大症是由于垂体前叶分泌过多生长激素所引起，如发病在青春期以后，骨骺已融合时，则表现为肢端肢大症;如起病在青春期前，骨骺尚未融合，则表现为巨人症;如起病在青春期，成人后仍继续发展，则表现为肢端肥大性巨人症。但是，关于巨人症和肢端肥大症的遗传因素知之甚少。[pdf download] 近期，Drs. Trivellin和他的团队，在新英格兰杂志上发表了他们的研究成果。他们从43名巨

巨人症及肢端肥大症是由于垂体前叶分泌过多生长激素所引起，如发病在青春期以后，骨骺已融合时，则表现为肢端肢大症;如起病在青春期前，骨骺尚未融合，则表现为巨人症;如起病在青春期，成人后仍继续发展，则表现为肢端肥大性巨人症。但是，关于巨人症和肢端肥大症的遗传因素知之甚少。[pdf download]

近期，Drs. Trivellin和他的团队，在新英格兰杂志上发表了他们的研究成果。他们从43名巨人症的患者中获取了临床和遗传研究的样本，然后在248名肢端肥大症的患者中，将相关的基因进行测序。


结果显示：13个巨人症患者的Xq26.3染色体出现微重复。在这13个样本中，有4例来自两个不相关的家族，9例是来自散发病例人群。出现Xq26.3染色体微重复的患者均在幼儿时期发病。而不携带Xq26.3染色体微重复的巨人症患者，均不在5岁之前发病。染色体Xq26.3基因特性，提示这些微重复是在染色体复制过程中产生的，其中包括四个编码蛋白基因。其中只有一个，GPR101基因(编码G蛋白偶联受体)，在垂体疾病中过度表达。他们还发现在248名肢端肥大症的患者中，有11名患者反复出现GPR101基因突变，而之前认为这些突变大多见于肿瘤疾病。当把GPR101突变基因转染入小鼠的GH3细胞时，小鼠就会出现生长激素的分泌增加及分泌生长激素的细胞的增殖。

最后Drs. Trivellin和他的团队认为，他们解释了一种儿科疾病(称作与X染色体相关的早期巨人症X-LAG)是由Xq26.3染色体重复变异引起的，由于生长激素的过度表达，在儿童期表现为巨人症。此外，GPR101基因的重复变异很可能也可以引起X-LAG。GPR101基因的反复突变在某些成年人，表现为肢端肥大症。

原始出处：

Trivellin G, Daly AF, Faucz FR, et al.Gigantism and Acromegaly Due to Xq26 Microduplications and GPR101 Mutation. N Engl J Med. 2014 Dec 18;371(25):2363-74. doi: 10.1056/NEJMoa1408028. Epub 2014 Dec 3[pdf download]


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    2015-10-11 hlycom3356

    感谢作者分享

    0

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    2015-06-08 ljjj1053

    好好学习学习

    0

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    2015-06-13 1249859em38(暂无昵称)

    #巨人症#

    0

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    2015-01-31 654699882_84926994

    #肢端肥大#

    0

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    2015-01-06 chg121

    #肢端肥大症#

    0

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    2015-01-06 新生儿张玉军

    #染色体#

    0

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New Engl J Med：患巨人症和肢端肥大是因为基因突变？

生长是由一系列激素经过复杂的调控程序而导致的，这些激素来源于下丘脑，垂体和外周组织。遗传性疾病会引起生长激素分泌增加，导致肢端肥大。如果在骨骺闭合之前生长激素过度分泌，就会引起儿童型巨人症。非综合征型巨人症是由腺垂体的分泌紊乱所导致的，通常表现为家族性孤立垂体腺瘤或偶发垂体腺瘤。目前生长激素所导致的儿童巨人症和成人指端肥大的发病率正在上升，但是对于巨人症和肢端肥大症遗传学基础的认识还不够充分。为了