MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh EH4 2XU, UK.
Genes Dev. 2011 Oct 1;25(19):2011-24. doi: 10.1101/gad.169037.
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.
物种之间最大的差异是大小；然而，决定生物体生长的发育机制仍知之甚少。原始侏儒症是一组具有极端全球生长失败的人类单基因疾病（包括 Seckel 综合征、小头骨发育不良性原始侏儒症 I [MOPD] 型 I 和 II 以及 Meier-Gorlin 综合征）。现在已经确定了十个与小头原始侏儒症相关的基因，这些基因编码参与基本细胞过程的蛋白质，包括基因组复制（ORC1[起始识别复合物 1]、ORC4、ORC6、CDT1 和 CDC6）、DNA 损伤反应（ATR[共济失调-毛细血管扩张和 Rad3 相关]）、mRNA 剪接（U4atac）和中心体功能（CEP152、PCNT 和 CPAP）。在这里，我们综述了这些疾病发病机制的细胞和发育机制，并探讨了对这些基因的进一步研究是否能为生物体生长的生理调节提供新的见解。
