Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies

L. E. Warner, P. Mancias, I. J. Butler, Craig M McDonald, L. Keppen, K. G. Koob, J. R. Lupski

Research output: Contribution to journalArticle

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Abstract

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; ref.7). 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).

Original languageEnglish (US)
Pages (from-to)382-384
Number of pages3
JournalNature Genetics
Volume18
Issue number4
DOIs
StatePublished - 1998
Externally publishedYes

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Mutation
Growth
Genes
Transcription Factors
Rhombencephalon
Immediate-Early Genes
Schwann Cells
Zinc Fingers
Peripheral Nervous System
Missense Mutation
Multigene Family
Myelin Sheath
Cell Differentiation
Tooth
Proteins
Cell Proliferation
DNA
Type 4E Charcot-Marie-Tooth disease

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Warner, L. E., Mancias, P., Butler, I. J., McDonald, C. M., Keppen, L., Koob, K. G., & Lupski, J. R. (1998). Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. Nature Genetics, 18(4), 382-384. https://doi.org/10.1038/ng0498-382

Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. / Warner, L. E.; Mancias, P.; Butler, I. J.; McDonald, Craig M; Keppen, L.; Koob, K. G.; Lupski, J. R.

In: Nature Genetics, Vol. 18, No. 4, 1998, p. 382-384.

Research output: Contribution to journalArticle

Warner, LE, Mancias, P, Butler, IJ, McDonald, CM, Keppen, L, Koob, KG & Lupski, JR 1998, 'Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies', Nature Genetics, vol. 18, no. 4, pp. 382-384. https://doi.org/10.1038/ng0498-382
Warner, L. E. ; Mancias, P. ; Butler, I. J. ; McDonald, Craig M ; Keppen, L. ; Koob, K. G. ; Lupski, J. R. / Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. In: Nature Genetics. 1998 ; Vol. 18, No. 4. pp. 382-384.
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