A large consanguineous family with a homozygous Metabotropic Glutamate Receptor 7 (mGlu7) variant and developmental epileptic encephalopathy: Effect on protein structure and ligand affinity.
Developmental epileptic encephalopathy
GRM7 gene
Next generation sequencing
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
17 07 2021
17 07 2021
Historique:
received:
11
03
2021
accepted:
11
07
2021
entrez:
18
7
2021
pubmed:
19
7
2021
medline:
6
8
2021
Statut:
epublish
Résumé
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. 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. 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. Our results contribute to a better understanding of the impact of GRM7 variants for the newly described associated phenotype.
Sections du résumé
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.
Identifiants
pubmed: 34273994
doi: 10.1186/s13023-021-01951-w
pii: 10.1186/s13023-021-01951-w
pmc: PMC8286605
doi:
Substances chimiques
Ligands
0
Receptors, Metabotropic Glutamate
0
metabotropic glutamate receptor 7
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
317Informations de copyright
© 2021. The Author(s).
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