Nature Genetics
18, 382 - 384 (1998)
doi:10.1038/ng0498-382
Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathiesLaura E. Warner1, Pedro Mancias2, Ian J. Butler2, Craig M. McDonald3, Laura Keppen4, K. Gene Koob5
& James R. Lupski1, 6, 7, 8
1Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
2Department of Neurology, University of Texas Health Science Center, Medical School, 6431 Fannin, Houston, Texas 77030, USA.
3Departments of Physical Medicine and Rehabilitation and Pediatrics, University of California Davis Medical Center, 4301 X Street, Sacramento, California 95817, USA.
4Department of Pediatrics and Adolescent Medicine, University of South Dakota School of Medicine, 1100 South Euclid, Sioux Falls, South Dakota 57117, USA.
5Neurology Associates, P. C., 911E. 20th Street, Suite 205, Sioux Falls, South Dakota 57105, USA.
6Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
7Texas Children's Hospital, Houston, Texas 77030, USA.
8e-mail: jlupski@bcm.tmc.edu 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 proliferation1,2. 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 factor3−6. Stable expression of Egr2 is specifically associated with the onset of myelination in the peripheral nervous system (PNS; ref.7). Egr2-/- mice display disrupted hindbrain segmentation and development8,9, and a block of Schwann-cell differentiation at an early stage10. 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).
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