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

Louise S. Bicknell, 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. OpitzPierre Sarda, Alison Ross, I. Karen Temple, Annick Toutain, Carol A. Wise, Michael Wright, Andrew P. Jackson

Research output: Contribution to journalArticle

149 Scopus citations

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 ears. 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.

Original languageEnglish (US)
Pages (from-to)356-360
Number of pages5
JournalNature genetics
Volume43
Issue number4
DOIs
StatePublished - Feb 2011

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Mutations in the pre-replication complex cause Meier-Gorlin syndrome'. Together they form a unique fingerprint.

  • Cite this

    Bicknell, L. S., Bongers, E. M. H. F., Leitch, A., Brown, S., Schoots, J., Harley, M. E., Aftimos, S., Al-Aama, J. Y., Bober, M., Brown, P. A. J., Van Bokhoven, H., Dean, J., Edrees, A. Y., Feingold, M., Fryer, A., Hoefsloot, L. H., Kau, N., Knoers, N. V. A. M., MacKenzie, J., ... Jackson, A. P. (2011). Mutations in the pre-replication complex cause Meier-Gorlin syndrome. Nature genetics, 43(4), 356-360. https://doi.org/10.1038/ng.775