Germline deletion of the miR-17∼92 cluster causes skeletal and growth defects in humans

被引：232

作者：

de Pontual, Loic ^{[1
,2
]}

Yao, Evelyn ^{[3
]}

Callier, Patrick ^{[4
]}

Faivre, Laurence ^{[4
]}

Drouin, Valerie ^{[5
]}

Cariou, Sandra ^{[1
]}

Van Haeringen, Arie ^{[6
]}

Genevieve, David ^{[7
]}

Goldenberg, Alice ^{[5
]}

Oufadem, Myriam ^{[1
]}

Manouvrier, Sylvie ^{[8
]}

Munnich, Arnold ^{[1
,9
,10
]}

Vidigal, Joana Alves ^{[3
]}

Vekemans, Michel ^{[1
]}

Lyonnet, Stanislas ^{[1
,9
,10
]}

Henrion-Caude, Alexandra ^{[1
]}

Ventura, Andrea ^{[3
]}

Amiel, Jeanne ^{[1
,9
,10
]}

机构：

[1] Univ Paris 05, Unite INSERM U781, Paris, France

[2] Univ Paris 13, Hop Jean Verdier, AP HP, Serv Pediat, Bondy, France

[3] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA

[4] Hop Enfants, Serv Genet, Dijon, France

[5] Hop Charles Nicolle, Serv Genet, Rouen, France

[6] Leiden Univ Med Ctr, Dept Human & Clin Genet, Leiden, Netherlands

[7] Hop Arnaud de Villeneuve, Serv Genet, Montpellier, France

[8] Hop J de Flandre, Serv Genet Clin, Lille, France

[9] Hop Necker Enfant Malades, AP HP, Serv Genet, Paris, France

[10] Hop Necker Enfant Malades, AP HP, Cytogenet Serv, Paris, France

来源：

NATURE GENETICS | 2011年 / 43卷 / 10期

基金：

美国国家卫生研究院;

关键词：

N-MYC; MICRORNA CLUSTER; FEINGOLD-SYNDROME; GENE; AMPLIFICATION; POLYCISTRON; DISSECTION; EXPRESSION; PHENOTYPE; MIR-17-92;

D O I：

10.1038/ng.915

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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(1), 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 of MIR17HG, encoding the miR-17 similar to 92 polycistronic miRNA cluster, in individuals with microcephaly, short stature and digital abnormalities. We demonstrate that haploinsufficiency of miR-17 similar to 92 is responsible for these developmental abnormalities by showing that mice harboring targeted deletion of the miR-17 similar to 92 cluster phenocopy several key features of the affected humans. These findings identify a regulatory function for miR-17 similar to 92 in growth and skeletal development and represent the first example of an miRNA gene responsible for a syndromic developmental defect in humans.

引用

页码：1026 / U146

页数：6

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