title: EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy.
abstract: Heterozygous mutations in the early growth response gene 2 (EGR2), which encodes a zinc-finger transcription factor that regulates the late stages of myelination, cause myelinopathies including congenital hypomyelinating neuropathy, Dejerine-Sottas neuropathy (DSN), and Charcot-Marie-Tooth disease type 1. We screened 170 unrelated neuropathy patients without mutations involving the peripheral myelin protein 22 gene (PMP22), the myelin protein zero gene (MPZ), or the gap junction protein beta1 gene (GJB1) and identified two DSN patients with the heterozygous mutation R359W in the alpha-helix domain of the first zinc-finger of EGR2. We now report that this mutation is a recurrent cause of DSN, and that expressivity ranges from that typical for DSN to a more rapidly progressive neuropathy that can cause death by age 6 years. Furthermore, in contrast to patients with typical DSN, patients with the EGR2 R359W mutation have more respiratory compromise and cranial nerve involvement.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Boerkoel
authors.forename: H
authors.initials: H
authors.lastname: Takashima
authors.forename: C A
authors.initials: CA
authors.lastname: Bacino
authors.forename: D
authors.initials: D
authors.lastname: Daentl
authors.forename: J R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D019943:Amino Acid Substitution; D018899:CpG Islands / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D051767:Early Growth Response Protein 2; D005091:Exons; D005260:Female; D005799:Genes, Dominant; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D016335:Zinc Fingers
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2; D014157:Transcription Factors; D004247:DNA