Whole Exon Deletion in the GFAP Gene Is a Novel Molecular Mechanism Causing Alexander Disease
| Autor: | Eamonn Sheridan, Anne Marie Childs, Dan Warren, Helen McCullagh, Ian R. Berry, Katrina Prescott, Lydia Green, Nick Camm, Marjo S. van der Knaap, Ian Craven, John H. Livingston, Sandhya Jose |
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| Přispěvatelé: | Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Pediatric surgery, Amsterdam Reproduction & Development (AR&D) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Tomography Scanners X-Ray Computed Mutant DNA Mutational Analysis macromolecular substances medicine.disease_cause 03 medical and health sciences Exon 0302 clinical medicine Glial Fibrillary Acidic Protein medicine Missense mutation Humans Child Exome sequencing Mutation Glial fibrillary acidic protein biology business.industry Leukodystrophy Brain General Medicine Exons medicine.disease Molecular biology Magnetic Resonance Imaging Alexander disease 030104 developmental biology nervous system Child Preschool Pediatrics Perinatology and Child Health biology.protein Neurology (clinical) Alexander Disease business 030217 neurology & neurosurgery Gene Deletion Follow-Up Studies |
| Zdroj: | Neuropediatrics, 49(2), 118-122. Hippokrates Verlag GmbH Green, L, Berry, I R, Childs, A M, Mccullagh, H, Jose, S, Warren, D, Craven, I, Camm, N, Prescott, K, van der Knaap, M S, Sheridan, E & Livingston, J H 2018, ' Whole Exon Deletion in the GFAP Gene Is a Novel Molecular Mechanism Causing Alexander Disease ', Neuropediatrics, vol. 49, no. 2, pp. 118-122 . https://doi.org/10.1055/s-0037-1608921 |
| ISSN: | 0174-304X |
| DOI: | 10.1055/s-0037-1608921 |
| Popis: | Alexander disease (AD) is a leukodystrophy caused by heterozygous mutations in the gene encoding the glial fibrillary acidic protein (GFAP). Currently, de novo heterozygous missense mutations in the GFAP gene are identified in over 95% of patients with AD. However, patients with biopsy-proven AD have been reported in whom no GFAP mutation has been identified. We report identical twin boys presenting in infancy with seizures and developmental delay in whom MR appearances were suggestive of AD with the exception of an unusual, bilateral, arc of calcification at the frontal white–gray junction. Initial mutation screening of the GFAP gene did not identify a mutation. Whole exome sequencing in both brothers revealed a de novo heterozygous in-frame deletion of the whole of exon 5 of the GFAP gene. Mutations in the GFAP gene are thought to result in a toxic effect of mutant GFAP disrupting the formation of the normal intermediate filament network and resulting in Rosenthal fiber formation, which has hitherto not been linked to exonic scale copy number variants in GFAP. Further studies on mutation negative AD patients are warranted to determine whether a similar mechanism underlies their disease. |
| Databáze: | OpenAIRE |
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