Novel missense mutation in the early growth response 2 gene associated with Dejerine–Sottas syndrome phenotype
Abstract
Background: Mutations in the early growth response 2 (EGR2) gene have recently been found in patients with congenital hypomyelinating neuropathy and Charcot-Marie-Tooth type 1 (CMT1) disease.
Objective: To determine the frequency of EGR2 mutations in patients with a diagnosis of CMT1, Dejerine–Sottas syndrome (DSS), or unspecified peripheral neuropathies.
Methods: Fifty patients and 70 normal control subjects were screened.
Results: A de novo missense mutation (Arg359Trp) in the α-helix of the first zinc-finger domain of the EGR2 transcription factor was identified in a patient diagnosed with a clinical phenotype consistent with DSS. This patient had a motor median nerve conduction velocity of 8 m/s. A sural nerve biopsy showed a severe loss of myelinated and unmyelinated fibers, evidence for demyelination, numerous classic onion bulbs, and focally folded myelin sheaths. DSS is a severe, childhood-onset demyelinating peripheral neuropathy initially thought to be inherited as an autosomal recessive trait. However, several dominant heterozygous mutations in the peripheral myelin protein 22 (PMP22) gene and dominant mutations in the peripheral myelin protein zero (MPZ) gene, both in the heterozygous and homozygous state, have been reported in patients with DSS.
Conclusions: Hereditary peripheral neuropathies represent a spectrum of disorders due to underlying defects in myelin structure or formation.
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Publication History
Received: September 16, 1998
Accepted: February 5, 1999
Published online: June 1, 1999
Published in print: June 1, 1999
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- EGR2 gene‐linked hereditary neuropathies present with a bimodal age distribution at symptoms onset , Journal of the Peripheral Nervous System, 28, 3, (359-367), (2023).https://doi.org/10.1111/jns.12572
- A novel PMP22 insertion mutation causing Charcot–Marie–Tooth disease type 3, Medicine, 100, 11, (e25163), (2021).https://doi.org/10.1097/MD.0000000000025163
- New evidence for secondary axonal degeneration in demyelinating neuropathies, Neuroscience Letters, 744, (135595), (2021).https://doi.org/10.1016/j.neulet.2020.135595
- A de novo EGR2 variant, c.1232A > G p.Asp411Gly, causes severe early-onset Charcot-Marie-Tooth Neuropathy Type 3 (Dejerine-Sottas Neuropathy), Scientific Reports, 9, 1, (2019).https://doi.org/10.1038/s41598-019-55875-4
- Schwann Cell and the Pathogenesis of Charcot–Marie–Tooth Disease, Myelin, (301-321), (2019).https://doi.org/10.1007/978-981-32-9636-7_19
- Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-coding RNA, Cell Reports, 20, 8, (1950-1963), (2017).https://doi.org/10.1016/j.celrep.2017.07.068
- EGR2 mutation enhances phenotype spectrum of Dejerine–Sottas syndrome, Journal of Neurology, 263, 7, (1456-1458), (2016).https://doi.org/10.1007/s00415-016-8153-9
- The EGR2 gene is involved in axonal Charcot−Marie−Tooth disease , European Journal of Neurology, 22, 12, (1548-1555), (2015).https://doi.org/10.1111/ene.12782
- Microprocessor Complex Subunit DiGeorge Syndrome Critical Region Gene 8 (Dgcr8) Is Required for Schwann Cell Myelination and Myelin Maintenance, Journal of Biological Chemistry, 290, 40, (24294-24307), (2015).https://doi.org/10.1074/jbc.M115.636407
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