Epileptic encephalopathy caused by ARV1 deficiency: Refinement of the genotype–phenotype spectrum and functional impact on GPI-anchored proteins
| Autor: | Anna C.E. Hurst, Christina Fagerberg, Lene Sperling, Marcello Scala, Lucas Herissant, Martine Doco-Fenzy, Emma Palmer, Beth Hudson, Melanie Jennesson, Martin Jakob Larsen, Elisabetta Amadori, Vincenzo Nigro, Andrea Accogli, Smrithi Salian, Pasquale Striano, Annalaura Torella, Michele Pinelli, Ieva Miceikaite, Megan Boothe, Valeria Capra, Tawfeg Ben-Omran, Mariasavina Severino, Thi Tuyet Mai Nguyen, Carlo Minetti, Rani Sachdev, Philippe M. Campeau |
|---|---|
| Přispěvatelé: | Salian, S., Scala, M., Nguyen, T. T. M., Severino, M., Accogli, A., Amadori, E., Torella, A., Pinelli, M., Hudson, B., Boothe, M., Hurst, A., Ben-Omran, T., Larsen, M. J., Fagerberg, C. R., Sperling, L., Miceikaite, I., Herissant, L., Doco-Fenzy, M., Jennesson, M., Nigro, V., Striano, P., Minetti, C., Sachdev, R. K., Palmer, E. E., Capra, V., Campeau, P. M. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Glycosylphosphatidylinositols DNA Mutational Analysis Mutant Infantile Spasms Transduction (genetics) 0302 clinical medicine Pregnancy Prenatal Diagnosis Genetics (clinical) 0303 health sciences Brain Magnetic Resonance Imaging Hypotonia Transmembrane protein GPI-anchored proteins Pedigree 3. Good health Phenotype Female medicine.symptom Spasms Infantile lentiviral gene rescue ARV1 early-infantile epileptic encephalopathy Alleles Amino Acid Substitution Carrier Proteins Facies GPI-Linked Proteins Humans Membrane Proteins Mutation Genetic Association Studies Genetic Predisposition to Disease Encephalopathy Biology 03 medical and health sciences Complementary DNA Genetics medicine 030304 developmental biology GPI-anchored protein Endoplasmic reticulum Wild type medicine.disease Molecular biology 030217 neurology & neurosurgery |
| Zdroj: | Salian, S, Scala, M, Nguyen, T T M, Severino, M, Accogli, A, Amadori, E, Torella, A, Pinelli, M, Hudson, B, Boothe, M, Hurst, A, Ben-Omran, T, Larsen, M J, Fagerberg, C R, Sperling, L, Miceikaite, I, Herissant, L, Doco-Fenzy, M, Jennesson, M, Nigro, V, Striano, P, Minetti, C, Sachdev, R K, Palmer, E E, Capra, V & Campeau, P M 2021, ' Epileptic encephalopathy caused by ARV1 deficiency : refinement of the genotype-phenotype spectrum and functional impact on GPI-anchored proteins ', Clinical Genetics, vol. 100, no. 5, pp. 607-614 . https://doi.org/10.1111/cge.14033 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|