ArticleOrphanet journal of rare diseases2013
Adult-onset Alexander disease, associated with a mutation in an alternative GFAP transcript, may be phenotypically modulated by a non-neutral HDAC6 variant.
Article in Orphanet journal of rare diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Genotype-Phenotype Association for 14Neurology. Genetics · 2025Article
- Characteristic MR Imaging Features and Serial Changes in Adult-Onset Alexander Disease: A Case Report.Journal of the Korean Society of Radiology · 2023Article
- Astrocyte phenotypes: Emphasis on potential markers in neuroinflammation.Histology and histopathology · 2021Review
- Parental Somatic Mosaicism Uncovers Inheritance of an ApparentlyFrontiers in genetics · 2021Article
- Type II Alexander disease caused by splicing errors and aberrant overexpression of an uncharacterized GFAP isoform.Human mutation · 2020Article
- Towards genomic database of Alexander disease to identify variations modifying disease phenotype.Scientific reports · 2019Article
- GFAP canonical transcript may not be suitable for the diagnosis of adult-onset Alexander disease.Acta neuropathologica communications · 2018Article
- Alexander Disease Mutations Produce Cells with Coexpression of Glial Fibrillary Acidic Protein and NG2 in Neurosphere Cultures and Inhibit Differentiation into Mature Oligodendrocytes.Frontiers in neurology · 2017Article
- Alexander disease in a dog: case presentation of electrodiagnostic, magnetic resonance imaging and histopathologic findings with review of literature.BMC veterinary research · 2015Review
- Review
- Progress and challenges in the computational prediction of gene function using networks: 2012-2013 update.F1000Research · 2013Article
- Psychiatric Onset Alexander Disease: An Important Challenge in Neuropsychiatric Diagnosis: A Case Report.Basic and clinical neuroscienceArticle
- GFAP at 50.ASN neuroReview
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundWe studied a family including two half-siblings, sharing the same mother, affected by slowly progressive, adult-onset neurological syndromes. In spite of the diversity of the clinical features, characterized by a mild movement disorder with cognitive impairment in the elder patient, and severe motor-neuron disease (MND) in her half-brother, the brain Magnetic Resonance Imaging (MRI) features were compatible with adult-onset Alexander's disease (AOAD), suggesting different expression of the same, genetically determined, condition.
methodsSince mutations in the alpha isoform of glial fibrillary acidic protein, GFAP-α, the only cause so far known of AOAD, were excluded, we applied exome Next Generation Sequencing (NGS) to identify gene variants, which were then functionally validated by molecular characterization of recombinant and patient-derived cells.
resultsExome-NGS revealed a mutation in a previously neglected GFAP isoform, GFAP-ϵ, which disrupts the GFAP-associated filamentous cytoskeletal meshwork of astrocytoma cells. To shed light on the different clinical features in the two patients, we sought for variants in other genes. The male patient had a mutation, absent in his half-sister, in X-linked histone deacetylase 6, a candidate MND susceptibility gene.
conclusionsExome-NGS is an unbiased approach that not only helps identify new disease genes, but may also contribute to elucidate phenotypic expression.
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