Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin syndrome

作者：Guernsey Duane L; Matsuoka Makoto; Jiang Haiyan; Evans Susan; Macgillivray Christine; Nightingale Mathew; Perry Scott; Ferguson Meghan; LeBlanc Marissa; Paquette Jean; Patry Lysanne; Rideout Andrea L; Thomas Aidan; Orr Andrew; McMaster Chris R; Michaud Jacques L; Deal Cheri; Langlois Sylvie; Superneau Duane W; Parkash Sandhya; Ludman Mark; Skidmore David L; Samuels Mark E^*

来源：Nature Genetics, 2011, 43(4): 360-U157.

DOI：10.1038/ng.777

Meier-Gorlin syndrome is a rare autosomal recessive genetic condition whose primary clinical hallmarks include small stature, small external ears and small or absent patellae. Using marker-assisted mapping in multiple families from a founder population and traditional coding exon sequencing of positional candidate genes, we identified three different mutations in the gene encoding ORC4, a component of the eukaryotic origin recognition complex, in five individuals with Meier-Gorlin syndrome. In two such individuals that were negative for mutations in ORC4, we found potential mutations in ORC1 and CDT1, two other genes involved in origin recognition. ORC4 is well conserved in eukaryotes, and the yeast equivalent of the human ORC4 missense mutation was shown to be pathogenic in functional assays of cell growth. This is the first report, to our knowledge, of a germline mutation in any gene of the origin recognition complex in a vertebrate organism.

• 出版日期2011-4