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.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
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 JA,Vekemans M,Lyonnet S,Henrion-Caude A,Ventura A,Amiel Jdoi
10.1038/ng.915subject
Has Abstractpub_date
2011-09-04 00:00:00pages
1026-30issue
10eissn
1061-4036issn
1546-1718pii
ng.915journal_volume
43pub_type
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