Germline deletion of the miR-17∼92 cluster causes skeletal and growth defects in humans.
Germline deletion of the miR-17∼92 cluster causes skeletal and growth defects in humans.
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DOI：
10.1038/ng.915
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发表时间：
2011-09-04
期刊：
影响因子：
30.8
通讯作者：
Amiel, Jeanne
中科院分区：
文献类型：
--
作者：
de Pontual, Loic;Yao, Evelyn;Callier, Patrick;Faivre, Laurence;Drouin, Valerie;Cariou, Sandra;Van Haeringen, Arie;Genevieve, David;Goldenberg, Alice;Oufadem, Myriam;Manouvrier, Sylvie;Munnich, Arnold;Vidigal, Joana Alves;Vekemans, Michel;Lyonnet, Stanislas;Henrion-Caude, Alexandra;Ventura, Andrea;Amiel, Jeanne
microRNAs（miRNAs）是动植物基因表达的关键调控因子。在多种模式生物中的研究表明，miRNA调节发育过程。据我们所知，已知由miRNA引起的唯一遗传性疾病是一种成人发病的非综合征性耳聋，目前还没有发现miRNA突变与人类的任何发育缺陷有关。在此，我们报告了在患有小头畸形、身材矮小和手指畸形的个体中，MIR 17 HG（编码miR-17 β 92多顺反子miRNA簇）的生殖系半合子缺失的鉴定。我们证明了miR-17 miR 92的单倍不足是这些发育异常的原因，通过显示携带miR-17 miR 92的靶向缺失的小鼠簇受影响人类的几个关键特征的表型。这些发现确定了miR-17 β 92在生长和骨骼发育中的调节功能，并代表了导致人类综合征性发育缺陷的miRNA基因的第一个例子。
MicroRNAs (miRNAs) are key regulators of gene expression in animals and plants. Studies in a variety of model organisms show that miRNAs modulate developmental processes. To our knowledge, the only hereditary condition known to be caused by a miRNA is a form of adult-onset non-syndromic deafness, and no miRNA mutation has yet been found to be responsible for any developmental defect in humans. Here we report the identification of germline hemizygous deletions ofMIR17HG, encoding the miR-17∼92 polycistronic miRNA cluster, in individuals with microcephaly, short stature and digital abnormalities. We demonstrate that haploinsufficiency of miR-17∼92 is responsible for these developmental abnormalities by showing that mice harboring targeted deletion of the miR-17∼92 cluster phenocopy several key features of the affected humans. These findings identify a regulatory function for miR-17∼92 in growth and skeletal development and represent the first example of an miRNA gene responsible for a syndromic developmental defect in humans.
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1.9
作者：
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通讯作者：
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影响因子：
30.8
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