V42. De novo mutations in the FUS gene are a frequent cause of sporadic ALS in very young patients
| Autor: | T. Holger, Alexander E Volk, M. Nicolai, A. Janine, Albert C. Ludolph, Angela Rosenbohm, Annemarie Hübers, W. Just, C. Kubisch, Jochen H. Weishaupt, N. Bierbaumer, M. Kathrin, H. Josef, G. Ingrid, P. Nürnberg |
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| Rok vydání: | 2015 |
| Předmět: |
Oncology
medicine.medical_specialty Mutation Pathology medicine.diagnostic_test business.industry SOD1 medicine.disease_cause Very early onset Sensory Systems Neurology C9orf72 Physiology (medical) Internal medicine Cohort medicine Neurology (clinical) business Gene De novo mutations Genetic testing |
| Zdroj: | Clinical Neurophysiology. 126:e87 |
| ISSN: | 1388-2457 |
| Popis: | Background Mutations in C9orf72 and SOD1 account for most of the familial and late-onset sporadic ALS cases. Mutations in FUS can be identified in around 5% of FALS and 1% of overall sporadic ALS cases. Methods We screened a large cohort of 15 very early onset (onset age C9orf72 , SOD1 and FUS in this distinct patient cohort. Results In the cohort of the very early onset patients, we identified 6 subjects (40.0%) carrying a FUS mutation. Genetic testing of the patients’ parents was possible in 5 families and revealed that the mutation in these individuals arose de novo . Two of the identified mutations had not been described before (c.1484delG; c.1504delG). Three patients carried the already in younger ALS patients described FUS mutation p.P525L. No mutations were found in SOD1 , C9orf72 . Five of the six identified patients presented with rapidly progressive bulbar symptoms. Conclusion Our study identifies FUS mutations as the most frequent genetic cause in early-onset ALS and suggests that de novo FUS mutations may be more common for sporadic ALS cases than recognized so far. Genetic testing of the FUS gene seems worthwhile in early onset ALS patients showing predominant bulbar symptoms and an aggressive disease course. |
| Databáze: | OpenAIRE |
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