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초록

Objective: Early growth response protein 2 (EGR2) is a crucial transcription factor involved in peripheral nerve myelination. Mutations in EGR2 have been reported to cause severe forms of demyelinating neuropathy, including Charcot-Marie-Tooth disease type 1D (CMT1D), although the clinical phenotype may vary depending on the specific mutation site. In this study, we aimed to characterize the clinical, electrophysiological, and neuroimaging phenotypes of Korean Charcot-Marie-Tooth disease (CMT) patients and to identify EGR2 mutations through genetic analysis.Methods: Whole exome sequencing was conducted on CMT patients to identify pathogenic genetic variants. Clinical evaluations included neurological examinations, motor and sensory nerve conduction studies, and magnetic resonance imaging (MRI) analysis of the lower limbs in patients harboring EGR2 mutations. In silico analyses were performed to assess the potential functional impacts of the identified mutations on the EGR2 protein structure.Results: Four EGR2 mutations were identified, including the novel p.D355E variant. Patients carrying the p.R359W, p.R381H, and p.R381L mutations exhibited early onset and rapid progression of symptoms, whereas the patient with the p.D355E mutation presented with symptom onset in the late 30s and demonstrated milder clinical manifestations into their 40s. MRI findings in the p.D355E patient suggested preservation of deep posterior compartment muscles, contrasting with observations in other mutation cases. In silico predictions indicated that the p.D355E mutation is likely to result in less pronounced structural changes in EGR2, potentially explaining the observed phenotypic differences.Conclusion: This study demonstrates that clinical variability among EGR2 mutations is correlated with the characteristics and positions of amino acid substitutions. Our findings contribute to the expanding database of EGR2 mutations, enhancing the understanding of diagnosis and prognosis in demyelinating neuropathies.

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