EGR2

SUMMARY:
Therefore, it seemed that the EGR2 mutations could cause not only the known demyelinating type and axonal type but also mixed-type CMT. Our findings expanded the phenotypic heterogeneities of EGR2-associated neuropathy.

TITLE:
EGR2-related mixed demyelinating and axonal Charcot-Marie-Tooth disease: An electrodiagnostic, nerve imaging, and histological study

DESCRIPTION:
CONCLUSION: Therefore, it seemed that the EGR2 mutations could cause not only the known demyelinating type and axonal type but also mixed-type CMT. Our findings expanded the phenotypic heterogeneities of EGR2-associated neuropathy.

CONTENT:
Clin Neuropathol. 2022 Jun 30. doi: 10.5414/NP301460. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The early growth response 2 gene (EGR2) mutations are associated with a group of hereditary neuropathy, including axonal neuropathy and hypomyelinating neuropathy or Charcot-Marie-Tooth disease (CMT) type 1D. We aim to perform an electrodiagnostic, nerve imaging, and histological study of EGR2-associated neuropathy.

MATERIALS AND METHODS: We performed a retrospective analysis of two patients with EGR2-related neurology at our hospital. The neuropathy was confirmed by the nerve conduction study. Nerve imaging and sural biopsies were performed in two patients.

RESULTS: Two unrelated boys exhibited early-onset length-dependent neuropathy. Next generation sequencing identified EGR2 gene with previously described E412K mutation in the third zine finger domain in patient 1 and a previously undescribed variant D355N mutation in the first zinc finger domain in patient 2. The magnetic resonance imaging of the lumbosacral plexus showed no abnormalities in patient 1 and thickened lumbosacral plexuses in patient 2. Electrophysiology and nerve biopsies showed a prominent axonal neuropathy, accompanied with demyelinating involvement.

CONCLUSION: Therefore, it seemed that the EGR2 mutations could cause not only the known demyelinating type and axonal type but also mixed-type CMT. Our findings expanded the phenotypic heterogeneities of EGR2-associated neuropathy.

PMID:35770518 | DOI:10.5414/NP301460

SOURCE:
Clinical neuropathology

TAGS:
EGR2

CATEGORY:
Research

SUBCATEGORY:
n/a

DATE – PUBLISHED:
2022-06-30T08:04:57Z

DATE – DOI: 2022-06-30T08:04:57Z
DATE – PUBMED: 2022 Jun 30
DATE OUTPUT MATCHED: True

DATE – ADDED:
Thu, 30 Jun 2022 06:00:00 -0400

DATE – RETRIEVED:
06/30/22 07:02AM
2022-06-30T07:02:09-04:00

FEATURED IMAGE:
Media Uploaded (image/png)

IDENTIFIER:
pmid:35770518,doi:10.5414/NP301460

PUBMED ID:
pubmed:35770518

DOI:
10.5414/NP301460

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/35770518/

LINK – DOI:
https://doi.org/10.5414/NP301460

LINK – PUBLISHER:
https://www.dustri.com/index.php?id=8&artId=189563&doi=10.5414/NP301460

REFERENCES:
CMT Treatment Report, Urgent Research, 2022-06-30T07:02:09-04:00, https://www.cmttreatmentreport.com.

https://www.nature.com/articles/s41598-019-55875-4

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920433/

https://www.ncbi.nlm.nih.gov/pubmed/31852952?dopt=Abstract

EGR2 mutation causes severe early-onset Charcot-Marie-Tooth Neuropathy Type 3 (Dejerine-Sottas Neuropathy).

A de novo EGR2 variant, c.1232A > G p.Asp411Gly, causes severe early-onset Charcot-Marie-Tooth Neuropathy Type 3 (Dejerine-Sottas Neuropathy).

Sci Rep. 2019 Dec 18;9(1):19336

Authors: Grosz BR, Golovchenko NB, Ellis M, Kumar K, Nicholson GA, Antonellis A, Kennerson ML

Abstract

EGR2 (early growth response 2) is a crucial transcription factor for the myelination of the peripheral nervous system. Mutations in EGR2 are reported to cause a heterogenous spectrum of peripheral neuropathy with wide variation in both severity and age of onset, including demyelinating and axonal forms of Charcot-Marie Tooth (CMT) neuropathy, Dejerine-Sottas neuropathy (DSN/CMT3), and congenital hypomyelinating neuropathy (CHN/CMT4E). Here we report a sporadic de novo EGR2 variant, c.1232A > G (NM_000399.5), causing a missense p.Asp411Gly substitution and discovered through whole-exome sequencing (WES) of the proband. The resultant phenotype is severe demyelinating DSN with onset at two years of age, confirmed through nerve biopsy and electrophysiological examination. In silico analyses showed that the Asp411 residue is evolutionarily conserved, and the p.Asp411Gly variant was predicted to be deleterious by multiple in silico analyses. A luciferase-based reporter assay confirmed the reduced ability of p.Asp411Gly EGR2 to activate a PMP22 (peripheral myelin protein 22) enhancer element compared to wild-type EGR2. This study adds further support to the heterogeneity of EGR2-related peripheral neuropathies and provides strong functional evidence for the pathogenicity of the p.Asp411Gly EGR2 variant.

PMID: 31852952 [PubMed – in process]

PubMed:31852952

Grosz BR, Golovchenko NB, Ellis M, Kumar K, Nicholson GA, Antonellis A, Kennerson ML