Mechanisms and pathways of growth failure in primordial dwarfism (original) (raw)

1. Andrew P. Jackson1
2. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh EH4 2XU, United Kingdom

Abstract

The greatest difference between species is size; however, the developmental mechanisms determining organism growth remain poorly understood. Primordial dwarfism is a group of human single-gene disorders with extreme global growth failure (which includes Seckel syndrome, microcephalic osteodysplastic primordial dwarfism I [MOPD] types I and II, and Meier-Gorlin syndrome). Ten genes have now been identified for microcephalic primordial dwarfism, encoding proteins involved in fundamental cellular processes including genome replication (ORC1 [origin recognition complex 1], ORC4, ORC6, CDT1, and CDC6), DNA damage response (ATR [ataxia-telangiectasia and Rad3-related]), mRNA splicing (U4atac), and centrosome function (CEP152, PCNT, and CPAP). Here, we review the cellular and developmental mechanisms underlying the pathogenesis of these conditions and address whether further study of these genes could provide novel insight into the physiological regulation of organism growth.

• DNA damage response
• DNA replication
• cell cycle; centrosome
• organism growth
• primordial dwarfism

Footnotes

• ↵1 Corresponding author.
  E-mail andrew.jackson{at}hgu.mrc.ac.uk.

• Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.169037.

• Copyright © 2011 by Cold Spring Harbor Laboratory Press

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