A Novel Mutation (D305V) in the early growth response 2 gene is associated with severe Charcot-Marie-Tooth type 1 disease

✍ Scribed by Emilia Bellone; Emilio Di Maria; Silvia Soriani; Alessandra Varese; Laura Lamba Doria; Franco Ajmar; Paola Mandich

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 18 KB
• Volume: 14
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/(sici)1098-1004(199910)14:4<353::aid-humu17>3.0.co;2-4

✦ Synopsis

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.