Warner L E, Mancias P, Butler I J, McDonald C M, Keppen L, Koob K G, Lupski J R
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Nat Genet. 1998 Apr;18(4):382-4. doi: 10.1038/ng0498-382.
The early growth response 2 gene (EGR2) is part of a multigene family encoding Cys2His2 type zinc-finger proteins and may play a role in the regulation of cellular proliferation. Egr2, (also known as Krox20) is the mouse orthologue of human EGR2 and was first identified as an immediate-early response gene, encoding a protein that binds DNA in a sequence-specific manner and acts as a transcription factor. Stable expression of Egr2 is specifically associated with the onset of myelination in the peripheral nervous system (PNS). Egr2(-/-) mice display disrupted hindbrain segmentation and development, and a block of Schwann-cell differentiation at an early stage. We hypothesized that Egr2 may be a transcription factor affecting late myelin genes and that human myelinopathies of the PNS may result from mutations in EGR2. In support of this hypothesis, we have identified one recessive and two dominant missense mutations in EGR2 (within regions encoding conserved functional domains) in patients with congenital hypomyelinating neuropathy (CHN) and a family with Charcot-Marie-Tooth type 1 (CMT1).
早期生长反应2基因（EGR2）是编码Cys2His2型锌指蛋白的多基因家族的一部分，可能在细胞增殖的调控中发挥作用。Egr2（也称为Krox20）是人类EGR2的小鼠同源物，最初被鉴定为即刻早期反应基因，编码一种以序列特异性方式结合DNA并作为转录因子起作用的蛋白质。Egr2的稳定表达与外周神经系统（PNS）髓鞘形成的开始特别相关。Egr2（-/-）小鼠表现出后脑节段化和发育紊乱，以及早期施万细胞分化受阻。我们推测Egr2可能是影响晚期髓鞘基因的转录因子，并且PNS的人类髓鞘病可能由EGR2的突变引起。为支持这一假设，我们在先天性低髓鞘性神经病（CHN）患者和一个1型遗传性运动感觉神经病（CMT1）家族中，在EGR2（在编码保守功能域的区域内）鉴定出一个隐性和两个显性错义突变。
