TY - JOUR
T1 - Epileptic encephalopathy caused by ARV1 deficiency
T2 - refinement of the genotype-phenotype spectrum and functional impact on GPI-anchored proteins
AU - Salian, Smrithi
AU - Scala, Marcello
AU - Nguyen, Thi Tuyet Mai
AU - Severino, Mariasavina
AU - Accogli, Andrea
AU - Amadori, Elisabetta
AU - Torella, Annalaura
AU - Pinelli, Michele
AU - Hudson, Beth
AU - Boothe, Megan
AU - Hurst, Anna
AU - Ben-Omran, Tawfeg
AU - Larsen, Martin J
AU - Fagerberg, Christina R
AU - Sperling, Lene
AU - Miceikaite, Ieva
AU - Herissant, Lucas
AU - Doco-Fenzy, Martine
AU - Jennesson, Mélanie
AU - Nigro, Vincenzo
AU - Striano, Pasquale
AU - Minetti, Carlo
AU - Sachdev, Rani K
AU - Palmer, Emma Elizabeth
AU - Capra, Valeria
AU - Campeau, Philippe M
N1 - This article is protected by copyright. All rights reserved.
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - ARV1
KW - GPI-anchored proteins
KW - early-infantile epileptic encephalopathy
KW - lentiviral gene rescue
U2 - 10.1111/cge.14033
DO - 10.1111/cge.14033
M3 - Journal article
C2 - 34296759
SN - 0009-9163
VL - 100
SP - 607
EP - 614
JO - Clinical Genetics
JF - Clinical Genetics
IS - 5
ER -