Germline deletion of the miR-17∼92 cluster causes skeletal and growth defects in humans Journal Article
| Authors: | De Pontual, L.; Yao, E.; Callier, P.; Faivre, L.; Drouin, V.; Cariou, S.; Van Haeringen, A.; Geneviève, D.; Goldenberg, A.; Oufadem, M.; Manouvrier, S.; Munnich, A.; Vidigal, J. A.; Vekemans, M.; Lyonnet, S.; Henrion-Caude, A.; Ventura, A.; Amiel, J. |
| Article Title: | Germline deletion of the miR-17∼92 cluster causes skeletal and growth defects in humans |
| Abstract: | 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 of MIR17HG, 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. © 2011 Nature America, Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; gene cluster; gene deletion; nonhuman; polymerase chain reaction; mouse; animals; mice; mice, knockout; mus; microrna; animal experiment; animal model; gene function; mice, inbred c57bl; short stature; animalia; pedigree; models, animal; germ line; embryo, mammalian; micrornas; germ-line mutation; growth disorder; bone defect; multigene family; databases, genetic; microcephaly; chromosome 13q; chromosomes, human, pair 13; haploinsufficiency; limb deformities, congenital; duodenal obstruction; microrna 17; brachydactyly; finger malformation; esophageal atresia; eyelids; musculoskeletal development |
| Journal Title: | Nature Genetics |
| Volume: | 43 |
| Issue: | 10 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2011-09-04 |
| Start Page: | 1026 |
| End Page: | 1031 |
| Language: | English |
| DOI: | 10.1038/ng.915 |
| PROVIDER: | scopus |
| PMCID: | PMC3184212 |
| PUBMED: | 21892160 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 November 2011" - "CODEN: NGENE" - "Source: Scopus" |
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