Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia
| Autor: | Sophie Tezenas du Montcel, Chantal M. E. Tallaksen, Stefan Vielhaber, Judith van Gaalen, Gabriella Silvestri, Sylvia Boesch, Jun-Suk Kang, Judith Machts, Ilaria Giordano, Florian Harmuth, Dagmar Timmann, Bart P.C. van de Warrenburg, Peter Bauer, Thomas Klopstock, Marc Sturm, Matthis Synofzik, Ludger Schöls, Christiane Neuhofer, Heike Jacobi, Marcella Masciullo, Christoph Kamm, Alessandro Filla, Christos Ganos, Thomas Klockgether, Ales Dudesek, Iselin M Wedding, Andreas Eigentler, Brigitte Katrin Paap |
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| Přispěvatelé: | Giordano, Ilaria, Harmuth, Florian, Jacobi, Heike, Paap, Brigitte, Vielhaber, Stefan, Machts, Judith, Schöls, Ludger, Synofzik, Matthi, Sturm, Marc, Tallaksen, Chantal, Wedding, Iselin M., Boesch, Sylvia, Eigentler, Andrea, Van De Warrenburg, Bart, Van Gaalen, Judith, Kamm, Christoph, Dudesek, Ale, Kang, Jun-Suk, Timmann, Dagmar, Silvestri, Gabriella, Masciullo, Marcella, Klopstock, Thoma, Neuhofer, Christiane, Ganos, Christo, Filla, Alessandro, Bauer, Peter, Tezenas Du Montcel, Sophie, Klockgether, Thomas |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Pathology Ataxia DNA Mutational Analysis Medizin medicine.disease_cause Severity of Illness Index Follow-Up Studie DNA Mutational Analysi physiopathology [Ataxia] 03 medical and health sciences 0302 clinical medicine Atrophy Internal medicine Severity of illness medicine Humans ddc:610 Aged Mutation Neurodegenerative Disease business.industry physiopathology [Neurodegenerative Diseases] Neurodegenerative Diseases genetics [Ataxia] Middle Aged Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] medicine.disease Europe Clinical trial Natural history Settore MED/26 - NEUROLOGIA Female Follow-Up Studies Neurology (clinical) 030104 developmental biology genetics [Neurodegenerative Diseases] Cohort Etiology medicine.symptom business 030217 neurology & neurosurgery Human |
| Zdroj: | Neurology, 89, 1043-1049 Neurology 89(10), 1043-1049 (2017). doi:10.1212/WNL.0000000000004311 Neurology, 89, 10, pp. 1043-1049 |
| ISSN: | 0028-3878 |
| DOI: | 10.1212/WNL.0000000000004311 |
| Popis: | Objective:To define the clinical phenotype and natural history of sporadic adult-onset degenerative ataxia and to identify putative disease-causing mutations.Methods:The primary measure of disease severity was the Scale for the Assessment and Rating of Ataxia (SARA). DNA samples were screened for mutations using a high-coverage ataxia-specific gene panel in combination with next-generation sequencing.Results:The analysis was performed on 249 participants. Among them, 83 met diagnostic criteria of clinically probable multiple system atrophy cerebellar type (MSA-C) at baseline and another 12 during follow-up. Positive MSA-C criteria (4.94 ± 0.74, p < 0.0001) and disease duration (0.22 ± 0.06 per additional year, p = 0.0007) were associated with a higher SARA score. Forty-eight participants who did not fulfill MSA-C criteria and had a disease duration of >10 years were designated sporadic adult-onset ataxia of unknown etiology/non-MSA (SAOA/non-MSA). Compared with MSA-C, SAOA/non-MSA patients had lower SARA scores (13.6 ± 6.0 vs 16.0 ± 5.8, p = 0.0200) and a slower annual SARA increase (1.1 ± 2.3 vs 3.3 ± 3.2, p = 0.0013). In 11 of 194 tested participants (6%), a definitive or probable genetic diagnosis was made.Conclusions:Our study provides quantitative data on the clinical phenotype and progression of sporadic ataxia with adult onset. Screening for causative mutations with a gene panel approach yielded a genetic diagnosis in 6% of the cohort.ClinicalTrials.gov registration:NCT02701036. |
| Databáze: | OpenAIRE |
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