Epileptic encephalopathy caused by ARV1 deficiency: Refinement of the genotype-phenotype spectrum and functional impact on GPI-anchored proteins.
Clin Genet
; 100(5): 607-614, 2021 11.
Article
en En
| MEDLINE
| ID: mdl-34296759
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fenotipo
/
Espasmos Infantiles
/
Predisposición Genética a la Enfermedad
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Estudios de Asociación Genética
/
Proteínas de la Membrana
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Female
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Humans
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Male
/
Pregnancy
Idioma:
En
Revista:
Clin Genet
Año:
2021
Tipo del documento:
Article
País de afiliación:
Canadá