title: A novel mutation (D305V) in the early growth response 2 gene is associated with severe Charcot-Marie-Tooth type 1 disease.
abstract: Hereditary motor and sensory neuropathies (HMSN) comprises a wide clinical spectrum of related disorders with defects in peripheral nerve myelination. Charcot-Marie-Tooth type 1 (CMT1) is the most common form and is usually a mild disease with onset in the first or second decade; however there is a interfamilial and intrafamilial clinical variation, ranging from asymptomatic expression to severe muscular weakness and atrophy. Recently point mutations in the early growth response 2 gene (EGR2/Krox-20) have been associated with hereditary myelinopathies. We investigated for mutations at the EGR2 gene a patient with severe CMT1 phenotype. Direct sequencing of EGR2 gene showed a heterozygous A T transversion at nucleotide 1064 that predicts an Asp305Val substitution within the first zinc-finger domain. The finding of a novel EGR2 mutation associated with a different phenotype confirms that peripheral neuropathies represent a continuum spectrum of related disorders due to an underlying defect in myelination.
authors.affiliation: Department of Oncology, Biology and Genetics, University of Genova, Genova; Italy
authors.forename: E
authors.initials: E
authors.lastname: Bellone
authors.forename: E
authors.initials: E
authors.lastname: Di Maria
authors.forename: S
authors.initials: S
authors.lastname: Soriani
authors.forename: A
authors.initials: A
authors.lastname: Varese
authors.forename: L L
authors.initials: LL
authors.lastname: Doria
authors.forename: F
authors.initials: F
authors.lastname: Ajmar
authors.forename: P
authors.initials: P
authors.lastname: Mandich
mesh_terms: D019943:Amino Acid Substitution; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002648:Child; D002886:Chromosomes, Human, Pair 17; D004268:DNA-Binding Proteins / Q000235:genetics*; D051767:Early Growth Response Protein 2; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2; D014157:Transcription Factors