Epileptic encephalopathy caused by ARV1 deficiency: Refinement of the genotype-phenotype spectrum and functional impact on GPI-anchored proteins.
Alleles
Amino Acid Substitution
Brain
/ abnormalities
Carrier Proteins
/ genetics
DNA Mutational Analysis
Facies
Female
GPI-Linked Proteins
/ biosynthesis
Genetic Association Studies
/ methods
Genetic Predisposition to Disease
Glycosylphosphatidylinositols
/ metabolism
Humans
Magnetic Resonance Imaging
Male
Membrane Proteins
/ deficiency
Mutation
Pedigree
Phenotype
Pregnancy
Prenatal Diagnosis
/ methods
Spasms, Infantile
/ diagnosis
ARV1
GPI-anchored proteins
early-infantile epileptic encephalopathy
lentiviral gene rescue
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
21
06
2021
received:
07
05
2021
accepted:
19
07
2021
pubmed:
24
7
2021
medline:
19
2
2022
entrez:
23
7
2021
Statut:
ppublish
Résumé
Early infantile epileptic encephalopathy 38 (EIEE38, MIM #617020) is caused by biallelic variants in ARV1, encoding a transmembrane protein of the endoplasmic reticulum with a pivotal role in glycosylphosphatidylinositol (GPI) biosynthesis. We ascertained seven new patients from six unrelated families harboring biallelic variants in ARV1, including five novel variants. Affected individuals showed psychomotor delay, hypotonia, early onset refractory seizures followed by regression and specific neuroimaging features. Flow cytometric analysis on patient fibroblasts showed a decrease in GPI-anchored proteins on the cell surface, supporting a lower residual activity of the mutant ARV1 as compared to the wildtype. A rescue assay through the transduction of lentivirus expressing wild type ARV1 cDNA effectively rescued these alterations. This study expands the clinical and molecular spectrum of the ARV1-related encephalopathy, confirming the essential role of ARV1 in GPI biosynthesis and brain function.
Substances chimiques
ARV1 protein, human
0
Carrier Proteins
0
GPI-Linked Proteins
0
Glycosylphosphatidylinositols
0
Membrane Proteins
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
607-614Subventions
Organisme : CIHR
Pays : Canada
Organisme : Fonds de Recherche du Québec - Santé
Organisme : Region of Southern Denmark
Informations de copyright
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
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