Evidence map›Paper›PMID 32337334›Full record

ArticleNeurology. Genetics2020

Novel EGR2 variant that associates with Charcot-Marie-Tooth disease when combined with lipopolysaccharide-induced TNF-α factor T49M polymorphism.

Maria Empar Blanco-Cantó, Nikiben Patel, Sergio Velasco-Aviles, Angeles Casillas-Bajo, Juan Salas-Felipe, Alexandre García-Escrivá, Carmen Díaz-Marín, Hugo Cabedo

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology. Genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 62% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Maria Empar Blanco-CantóISABIAL (FISABIO) (M.E.B.-C., N.P., S.V.-A., A.C.-B., C.D.-M., H.C.), Hospital General Universitario de Alicante; Instituto de Neurociencias de Alicante UMH-CSIC (N.P., S.V.-A., A.C.-B., H.C.), San Juan de Alicante, Spain; Hospital Marina Salud (J.S.-F.), Denia; and Hospital IMED Levante (A.G.-E.), Benidorm, Spain.
Nikiben PatelISABIAL (FISABIO) (M.E.B.-C., N.P., S.V.-A., A.C.-B., C.D.-M., H.C.), Hospital General Universitario de Alicante; Instituto de Neurociencias de Alicante UMH-CSIC (N.P., S.V.-A., A.C.-B., H.C.), San Juan de Alicante, Spain; Hospital Marina Salud (J.S.-F.), Denia; and Hospital IMED Levante (A.G.-E.), Benidorm, Spain.
Sergio Velasco-AvilesISABIAL (FISABIO) (M.E.B.-C., N.P., S.V.-A., A.C.-B., C.D.-M., H.C.), Hospital General Universitario de Alicante; Instituto de Neurociencias de Alicante UMH-CSIC (N.P., S.V.-A., A.C.-B., H.C.), San Juan de Alicante, Spain; Hospital Marina Salud (J.S.-F.), Denia; and Hospital IMED Levante (A.G.-E.), Benidorm, Spain.
Angeles Casillas-BajoISABIAL (FISABIO) (M.E.B.-C., N.P., S.V.-A., A.C.-B., C.D.-M., H.C.), Hospital General Universitario de Alicante; Instituto de Neurociencias de Alicante UMH-CSIC (N.P., S.V.-A., A.C.-B., H.C.), San Juan de Alicante, Spain; Hospital Marina Salud (J.S.-F.), Denia; and Hospital IMED Levante (A.G.-E.), Benidorm, Spain.
Juan Salas-FelipeISABIAL (FISABIO) (M.E.B.-C., N.P., S.V.-A., A.C.-B., C.D.-M., H.C.), Hospital General Universitario de Alicante; Instituto de Neurociencias de Alicante UMH-CSIC (N.P., S.V.-A., A.C.-B., H.C.), San Juan de Alicante, Spain; Hospital Marina Salud (J.S.-F.), Denia; and Hospital IMED Levante (A.G.-E.), Benidorm, Spain.
Alexandre García-EscriváISABIAL (FISABIO) (M.E.B.-C., N.P., S.V.-A., A.C.-B., C.D.-M., H.C.), Hospital General Universitario de Alicante; Instituto de Neurociencias de Alicante UMH-CSIC (N.P., S.V.-A., A.C.-B., H.C.), San Juan de Alicante, Spain; Hospital Marina Salud (J.S.-F.), Denia; and Hospital IMED Levante (A.G.-E.), Benidorm, Spain.
Carmen Díaz-MarínISABIAL (FISABIO) (M.E.B.-C., N.P., S.V.-A., A.C.-B., C.D.-M., H.C.), Hospital General Universitario de Alicante; Instituto de Neurociencias de Alicante UMH-CSIC (N.P., S.V.-A., A.C.-B., H.C.), San Juan de Alicante, Spain; Hospital Marina Salud (J.S.-F.), Denia; and Hospital IMED Levante (A.G.-E.), Benidorm, Spain.
Hugo CabedoISABIAL (FISABIO) (M.E.B.-C., N.P., S.V.-A., A.C.-B., C.D.-M., H.C.), Hospital General Universitario de Alicante; Instituto de Neurociencias de Alicante UMH-CSIC (N.P., S.V.-A., A.C.-B., H.C.), San Juan de Alicante, Spain; Hospital Marina Salud (J.S.-F.), Denia; and Hospital IMED Levante (A.G.-E.), Benidorm, Spain.
Instituto de Neurociencias · ESHospital Marina Baixa · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo identify novel genetic mechanisms causing Charcot-Marie-Tooth (CMT) disease.

methodsWe performed a next-generation sequencing study of 34 genes associated with CMT in a patient with peripheral neuropathy.

resultsWe found a non-previously described mutation in EGR2 (p.P397H). P397H mutation is located within the loop that connects zinc fingers 2 and 3, a pivotal domain for the activity of this transcription factor. Using promoter activity luciferase assays, we found that this mutation promotes decreased transcriptional activity of EGR2. In this patient, we also found a previously described nonpathogenic polymorphism in lipopolysaccharide-induced TNF-α factor (LITAF) (p.T49M). We show that the p.T49M mutation decreases the steady-state levels of the LITAF protein in Schwann cells. Loss of function of LITAF has been shown to produce deregulation in the NRG1-erbB signaling, a pivotal pathway for EGR2 expression by Schwann cells. Surprisingly, our segregation study demonstrates that p.P397H mutation in EGR2 is not sufficient to produce CMT disease. Most notably, only those patients expressing simultaneously the LITAF T49M polymorphism develop peripheral neuropathy.

conclusionsOur data support that the LITAF loss-of-function interferes with the expression of the transcriptional-deficient EGR2 P397H mutant hampering Schwann cell differentiation and suggest that in vivo both genes act in tandem to allow the proper development of myelin.

Identifiers

PMID32337334
PMCPMC7164973
OpenAlexW3009783550

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.