A novel missense mutation in the early growth response 2 gene associated with late-onset Charcot--Marie--Tooth disease type 1.
A novel mutation (Arg381Cys) in the second zinc-finger domain of early growth response 2 (EGR2) was identified in a late-onset Charcot--Marie--Tooth disease type 1 (CMT1) patient. This patient had initial symptoms of numbness and weakness in the leg at age 59, and a median nerve motor conduction velocity of 27 m/s. A sural nerve biopsy showed a severe loss of myelinated fibers with numerous onion bulbs. This is the first report of the EGR2 mutation presenting a late onset of CMT1 phenotype. Its mutation was a different amino acid substitution at codon 381 (Arg381His) which demonstrated congenital hypomyelinating neuropathy or early-onset CMT1. This report suggests that the EGR2 mutation represents divergent phenotypes at codon 381, which may be a mutation hotspot.
Department of Neurology, Nagoya University School of Medicine, Nagoya 466, Japan.
T
T
Yoshihara
F
F
Kanda
M
M
Yamamoto
H
H
Ishihara
K
K
Misu
N
N
Hattori
K
K
Chihara
G
G
Sobue
D000368:Aged; D001706:Biopsy; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D051767:Early Growth Response Protein 2; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D013497:Sural Nerve / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2; D014157:Transcription Factors