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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2021

Open Access 01-12-2021 | Cranial MRI | Research

A large consanguineous family with a homozygous Metabotropic Glutamate Receptor 7 (mGlu7) variant and developmental epileptic encephalopathy: Effect on protein structure and ligand affinity

Authors: Marwa Ben Jdila, Cécile Mignon-Ravix, Sihem Ben Ncir, Fatma Kammoun, Faiza Fakhfakh, Laurent Villard, Chahnez Triki

Published in: Orphanet Journal of Rare Diseases | Issue 1/2021

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Abstract

Background

Developmental and epileptic encephalopathies (DEE) are chronic neurological conditions where epileptic activity contributes to the progressive disruption of brain function, frequently leading to impaired motor, cognitive and sensory development.

Patients and methods

The present study reports a clinical investigation and a molecular analysis by Next Generation Sequencing (NGS) of a large consanguineous family comprising several cases of developmental and epileptic encephalopathy. Bioinformatic prediction and molecular docking analysis were also carried out.

Results

The majority of patients in our studied family had severe developmental impairments, early-onset seizures, brain malformations such as cortical atrophy and microcephaly, developmental delays and intellectual disabilities. The molecular investigations revealed a novel homozygous variant c.1411G>A (p.Gly471Arg) in the GRM7 gene which was segregating with the disease in the family. Bioinformatic tools predicted its pathogenicity and docking analysis revealed its potential effects on mGlu7 protein binding to its ligand.

Conclusion

Our results contribute to a better understanding of the impact of GRM7 variants for the newly described associated phenotype.
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Metadata
Title
A large consanguineous family with a homozygous Metabotropic Glutamate Receptor 7 (mGlu7) variant and developmental epileptic encephalopathy: Effect on protein structure and ligand affinity
Authors
Marwa Ben Jdila
Cécile Mignon-Ravix
Sihem Ben Ncir
Fatma Kammoun
Faiza Fakhfakh
Laurent Villard
Chahnez Triki
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2021
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-021-01951-w

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