Spinocerebellar ataxia 17 (SCA17) and Huntington's disease-like 4 (HDL4)
| Autor: | Alexis Brice, Giovanni Stevanin |
|---|---|
| Přispěvatelé: | Aouinat, Farid, Neurologie et thérapeutique expérimentale, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC) |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Cerebellum
MESH: Spinocerebellar Ataxias MESH: TATA-Box Binding Protein Biology MESH: Phenotype Creutzfeldt-Jakob Syndrome MESH: Chromosomal Instability 03 medical and health sciences 0302 clinical medicine Huntington's disease Autosomal dominant cerebellar ataxia Alzheimer Disease Chromosomal Instability medicine MESH: Trinucleotide Repeat Expansion Humans Spinocerebellar Ataxias [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Allele Gene 030304 developmental biology Genetics 0303 health sciences MESH: Humans Parkinson Disease MESH: Creutzfeldt-Jakob Syndrome Spinocerebellar Degenerations medicine.disease TATA-Box Binding Protein Penetrance MESH: Huntington Disease MESH: Schizophrenia medicine.anatomical_structure Huntington Disease Phenotype Neurology Spinocerebellar ataxia Schizophrenia [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Neurology (clinical) Trinucleotide Repeat Expansion 030217 neurology & neurosurgery MESH: Alzheimer Disease MESH: Parkinson Disease |
| Zdroj: | The Cerebellum The Cerebellum, Springer, 2008, 7 (2), pp.170-8. ⟨10.1007/s12311-008-0016-1⟩ The Cerebellum, 2008, 7 (2), pp.170-8. ⟨10.1007/s12311-008-0016-1⟩ |
| ISSN: | 1473-4222 1473-4230 |
| DOI: | 10.1007/s12311-008-0016-1⟩ |
| Popis: | International audience; Spinocerebellar ataxia 17 (SCA17) or Huntington's disease-like-4 is a neurodegenerative disease caused by the expansion above 44 units of a CAG/CAA repeat in the coding region of the TATA box binding protein (TBP) gene leading to an abnormal expansion of a polyglutamine stretch in the corresponding protein. Alleles with 43 and 44 repeats have been identified in sporadic cases and their pathogenicity remains uncertain. Furthermore, incomplete penetrance of pathological alleles with up to 49 repeats has been suggested. The imperfect nature of the repeat makes intergenerational instability extremely rare and de novo mutations are most likely the result of partial duplications. This is one of the rarer forms of autosomal dominant cerebellar ataxia but the associated phenotype is often severe, involving various systems (cerebral cortex, striatum, and cerebellum), with extremely variable age at onset (range: 3-75 years) and clinical presentation. This gene is thought to account for a small proportion of patients with a Huntington's disease-like phenotype and cerebellar signs. Parkinson's disease-like, Creutzfeldt-Jakob disease-like and Alzheimer disease-like phenotypes have also been described with small SCA17 expansions. The abnormal protein is expressed at the same level as its normal counterpart and forms neuronal intranuclear inclusions containing other proteins involved in protein folding or degradation. The increase in the size of the glutamine stretch enhances transcription in vitro, probably leading to transcription deregulation. Interestingly, the TBP protein mutated in SCA17 is recruited in the inclusions of other polyglutaminopathies, suggesting its involvement in the transcription down-regulation observed in these diseases. |
| Databáze: | OpenAIRE |
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