Splice site, frameshift, and chimeric GFAP mutations in Alexander disease
| Autor: | Marjo S. van der Knaap, James M. Powers, Michael Brenner, Daniel Flint, John F. Mantovani, James E. Goldman, Albee Messing, Sakkubai Naidu, Josef Ekstein, Lital S. Webster, Rong Li, Edwin H. Kolodny, Alan K. Percy |
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| Přispěvatelé: | Other departments, Pediatric surgery, NCA - Childhood White Matter Diseases, Neuroscience Campus Amsterdam - Childhood White Matter Diseases |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male RNA Splicing Article Frameshift mutation Exon Glial Fibrillary Acidic Protein Genetics medicine Intermediate Filament Protein Coding region Humans Intermediate filament Frameshift Mutation Gene Genetics (clinical) Glial fibrillary acidic protein biology Infant Newborn Infant SDG 10 - Reduced Inequalities medicine.disease Molecular biology Alexander disease Astrocytes Mutation biology.protein Female Alexander Disease |
| Zdroj: | Flint, D, Li, R, Webster, L S, Naidu, S, Kolodny, E, Percy, A, van der Knaap, M S, Powers, J M, Mantovani, J F, Ekstein, J, Goldman, J E, Messing, A & Brenner, M 2012, ' Splice site, frameshift, and chimeric GFAP mutations in Alexander disease ', Human Mutation, vol. 33, no. 7, pp. 1141-1148 . https://doi.org/10.1002/humu.22094 Human mutation, 33(7), 1141-1148. Wiley-Liss Inc. Human Mutation, 33(7), 1141-1148. Wiley-Liss Inc. |
| ISSN: | 1059-7794 |
| DOI: | 10.1002/humu.22094 |
| Popis: | Alexander disease (AxD) is a usually fatal astrogliopathy primarily caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP), an intermediate filament protein expressed in astrocytes. We describe three patients with unique characteristics, and whose mutations have implications for AxD diagnosis and studies of intermediate filaments. Patient 1 is the first reported case with a noncoding mutation. The patient has a splice site change producing an in-frame deletion of exon 4 in about 10% of the transcripts. Patient 2 has an insertion and deletion at the extreme end of the coding region, resulting in a short frameshift. In addition, the mutation was found in buccal DNA but not in blood DNA, making this patient the first reported chimera. Patient 3 has a single-base deletion near the C-terminal end of the protein, producing a short frameshift. These findings recommend inclusion of intronic splice site regions in genetic testing for AxD, indicate that alteration of only a small fraction of GFAP can produce disease, and provide caution against tagging intermediate filaments at their C-terminal end for cell biological investigations. Hum Mutat 33:11411148, 2012. (c) 2012 Wiley Periodicals, Inc |
| Databáze: | OpenAIRE |
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