PMID- 10371530
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20190514
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 52
IP  - 9
DP  - 1999 Jun 10
TI  - Novel missense mutation in the early growth response 2 gene associated with 
      Dejerine-Sottas syndrome phenotype.
PG  - 1827-32
AB  - BACKGROUND: Mutations in the early growth response 2 (EGR2) gene have recently 
      been found in patients with congenital hypomyelinating neuropathy and 
      Charcot-Marie-Tooth type 1 (CMT1) disease. OBJECTIVE: To determine the frequency 
      of EGR2 mutations in patients with a diagnosis of CMT1, Dejerine-Sottas syndrome 
      (DSS), or unspecified peripheral neuropathies. METHODS: Fifty patients and 70 
      normal control subjects were screened. RESULTS: A de novo missense mutation 
      (Arg359Trp) in the alpha-helix of the first zinc-finger domain of the EGR2 
      transcription factor was identified in a patient diagnosed with a clinical 
      phenotype consistent with DSS. This patient had a motor median nerve conduction 
      velocity of 8 m/s. A sural nerve biopsy showed a severe loss of myelinated and 
      unmyelinated fibers, evidence for demyelination, numerous classic onion bulbs, 
      and focally folded myelin sheaths. DSS is a severe, childhood-onset demyelinating 
      peripheral neuropathy initially thought to be inherited as an autosomal recessive 
      trait. However, several dominant heterozygous mutations in the peripheral myelin 
      protein 22 (PMP22) gene and dominant mutations in the peripheral myelin protein 
      zero (MPZ) gene, both in the heterozygous and homozygous state, have been 
      reported in patients with DSS. CONCLUSIONS: Hereditary peripheral neuropathies 
      represent a spectrum of disorders due to underlying defects in myelin structure 
      or formation.
FAU - Timmerman, V
AU  - Timmerman V
AD  - Department of Molecular Genetics, Flanders Interuniversity Institute for 
      Biotechnology and Laboratory of Neurogenetics, Born-Bunge Foundation, University 
      of Antwerp, Belgium.
FAU - De Jonghe, P
AU  - De Jonghe P
FAU - Ceuterick, C
AU  - Ceuterick C
FAU - De Vriendt, E
AU  - De Vriendt E
FAU - Lofgren, A
AU  - Lofgren A
FAU - Nelis, E
AU  - Nelis E
FAU - Warner, L E
AU  - Warner LE
FAU - Lupski, J R
AU  - Lupski JR
FAU - Martin, J J
AU  - Martin JJ
FAU - Van Broeckhoven, C
AU  - Van Broeckhoven C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (EGR2 protein, human)
RN  - 0 (Early Growth Response Protein 2)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - DNA Mutational Analysis
MH  - DNA Primers
MH  - DNA-Binding Proteins/*genetics
MH  - Early Growth Response Protein 2
MH  - Hereditary Sensory and Motor Neuropathy/*genetics
MH  - Humans
MH  - Microscopy, Electron
MH  - Molecular Sequence Data
MH  - Mutation, Missense/*genetics
MH  - *Phenotype
MH  - Sural Nerve/ultrastructure
MH  - Time Factors
MH  - Transcription Factors/*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 - 10.1212/wnl.52.9.1827 [doi]
PST - ppublish
SO  - Neurology. 1999 Jun 10;52(9):1827-32. doi: 10.1212/wnl.52.9.1827.