PMID- 10369870
OWN - NLM
STAT- MEDLINE
DCOM- 19990816
LR  - 20191210
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 7
DP  - 1999 Jul
TI  - Functional consequences of mutations in the early growth response 2 gene (EGR2) 
      correlate with severity of human myelinopathies.
PG  - 1245-51
AB  - The early growth response 2 gene ( EGR2 ) is a Cys2His2zinc finger transcription 
      factor which is thought to play a role in the regulation of peripheral nervous 
      system myelination. This idea is based partly on the phenotype of homozygous 
      Krox20 ( Egr2 ) knockout mice, which display hypomyelination of the PNS and a 
      block of Schwann cells at an early stage of differentiation. Mutations in the 
      human EGR2 gene have recently been associated with the inherited peripheral 
      neuropathies Charcot-Marie-Tooth type 1, Dejerine-Sottas syndrome and congenital 
      hypomyelinating neuropathy. Three of the four EGR2 mutations are dominant and 
      occur within the zinc finger DNA-binding domain. The fourth mutation is recessive 
      and affects the inhibitory domain (R1) that binds the NAB transcriptional 
      co-repressors. A combination of DNA-binding assays and transcriptional analysis 
      was used to determine the functional consequences of these mutations. The zinc 
      finger mutations affect DNA binding and the amount of residual binding directly 
      correlates with disease severity. The R1 domain mutation prevents interaction of 
      EGR2 with the NAB co-repressors and thereby increases transcriptional activity. 
      These data provide insight into the possible disease mechanisms underlying EGR2 
      mutations and the reason for varying severity and differences in inheritance 
      patterns.
FAU - Warner, L E
AU  - Warner LE
AD  - Department of Molecular and Human Genetics, Baylor College of Medicine, Hoston, 
      TX 77030, USA.
FAU - Svaren, J
AU  - Svaren J
FAU - Milbrandt, J
AU  - Milbrandt J
FAU - Lupski, J R
AU  - Lupski JR
LA  - eng
SI  - GENBANK/AF139463
GR  - HD94021/HD/NICHD NIH HHS/United States
GR  - P01 CA49712-08/CA/NCI NIH HHS/United States
GR  - R01 NS27042/NS/NINDS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (EGR2 protein, human)
RN  - 0 (Early Growth Response Protein 2)
RN  - 0 (Egr2 protein, mouse)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Charcot-Marie-Tooth Disease/genetics
MH  - Chlorocebus aethiops
MH  - DNA-Binding Proteins/*genetics
MH  - Demyelinating Diseases/*genetics
MH  - Early Growth Response Protein 2
MH  - Expressed Sequence Tags
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Transcription Factors/*genetics
MH  - Transcriptional Activation
MH  - Zinc Fingers/genetics
EDAT- 1999/06/17 00:00
MHDA- 1999/06/17 00:01
CRDT- 1999/06/17 00:00
PHST- 1999/06/17 00:00 [pubmed]
PHST- 1999/06/17 00:01 [medline]
PHST- 1999/06/17 00:00 [entrez]
AID - ddc130 [pii]
AID - 10.1093/hmg/8.7.1245 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Jul;8(7):1245-51. doi: 10.1093/hmg/8.7.1245.