FTLD-ALS of TDP-43 type and SCA2 in a family with a full ataxin-2 polyglutamine expansion
| Autor: | Bing Tseu, David A Hilton, Olaf Ansorge, Adam Zeman, Kevin Talbot, Dirk Bäumer, Simon East |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Pathology medicine.medical_specialty Ataxia DNA Mutational Analysis Nerve Tissue Proteins Neuropathology Biology Pathology and Forensic Medicine Cellular and Molecular Neuroscience mental disorders medicine Humans Spinocerebellar Ataxias Amyotrophic lateral sclerosis Aged 80 and over Family Health Genetic heterogeneity Amyotrophic Lateral Sclerosis nutritional and metabolic diseases Frontotemporal lobar degeneration medicine.disease nervous system diseases DNA-Binding Proteins Ataxins Ataxin Spinocerebellar ataxia Neurology (clinical) medicine.symptom Trinucleotide Repeat Expansion Trinucleotide repeat expansion |
| Zdroj: | Acta Neuropathologica. 128:597-604 |
| ISSN: | 1432-0533 0001-6322 |
| Popis: | Polyglutamine expansions in the ataxin-2 gene (ATXN2) cause autosomal dominant spinocerebellar ataxia type 2 (SCA2), but have recently also been associated with amyotrophic lateral sclerosis (ALS). We present clinical and pathological features of a family in which a pathological ATXN2 expansion led to frontotemporal lobar degeneration with ALS (FTLD-ALS) in the index case, but typical SCA2 in a son, and compare the neuropathology with a case of typical SCA2. The index case shares the molecular signature of SCA2 with prominent polyglutamine and p62-positive intranuclear neuronal inclusions mainly in the pontine nuclei, while harbouring more pronounced neocortical and spinal TDP-43 pathology. We conclude that ATXN2 mutations can cause not only ALS, but also a neuropathological overlap syndrome of SCA2 and FTLD presenting clinically as pure FTLD-ALS without ataxia. The cause of the phenotypic heterogeneity remains unexplained, but the presence of a CAA-interrupted CAG repeat in the FTLD case in this family suggests that one potential mechanism may be variation in repeat tract composition between members of the same family. |
| Databáze: | OpenAIRE |
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