Mutations in the pre-replication complex cause Meier-Gorlin syndrome

  • Nat Genet. 2011 Feb 27;43(4):356-9. doi: 10.1038/ng.775.
Louise S Bicknell  1 ,  Ernie M H F Bongers ,  Andrea Leitch ,  Stephen Brown ,  Jeroen Schoots ,  Margaret E Harley ,  Salim Aftimos ,  Jumana Y Al-Aama ,  Michael Bober ,  Paul A J Brown ,  Hans van Bokhoven ,  John Dean ,  Alaa Y Edrees ,  Murray Feingold ,  Alan Fryer ,  Lies H Hoefsloot ,  Nikolaus Kau ,  Nine V A M Knoers ,  James Mackenzie ,  John M Opitz ,  Pierre Sarda ,  Alison Ross ,  I Karen Temple ,  Annick Toutain ,  Carol A Wise ,  Michael Wright ,  Andrew P Jackson
Affiliations
  • 1. Medical Research Council (MRC) Human Genetics Unit (HGU), Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
PMID: 21358632 DOI: 10.1038/ng.775
Abstract

Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears¹⁻³. Both pre- and post-natal growth are impaired in this disorder, and although microcephaly is often evident, intellect is usually normal in this syndrome. We report here that individuals with this disorder show marked locus heterogeneity, and we identify mutations in five separate genes: ORC1, ORC4, ORC6, CDT1 and CDC6. All of these genes encode components of the pre-replication complex, implicating defects in replication licensing as the cause of a genetic syndrome with distinct developmental abnormalities.