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

156 0
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2015-06-08 ljjj1053

好好学习学习

171 0
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2015-06-13 1249859em38(暂无昵称)

#巨人症#

67 0
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2015-01-31 654699882_84926994

#肢端肥大#

65 0
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2015-01-06 chg121

#肢端肥大症#

75 0
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2015-01-06 新生儿张玉军

#染色体#

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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

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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

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New Engl J Med：患巨人症和肢端肥大是因为基因突变？

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