دورية أكاديمية
Molecular consequences of dominant Bethlem myopathy collagen VI mutations
| العنوان: | Molecular consequences of dominant Bethlem myopathy collagen VI mutations |
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| المؤلفون: | Baker, N., Morgelin, M., Pace, R., Peat, R., Adams, N., Gardner, R., Rowland, L., Miller, G., De Jonghe, P., Ceulemans, B., Hannibal, M., Edwards, M., Thompson, E., Jacobson, R., Quinlivan, R., Aftimos, S., Kornberg, A., North, K., Bateman, J., Lamande, S. |
| المصدر: | http://dx.doi.org/10.1002/ana.21213Test. |
| بيانات النشر: | Wiley-Liss |
| سنة النشر: | 2007 |
| المجموعة: | The University of Adelaide: Digital Library |
| مصطلحات موضوعية: | Humans, Muscular Diseases, Collagen Diseases, Genetic Predisposition to Disease, Collagen Type VI, Genes, Dominant, Mutation, Polymorphism, Single Nucleotide, Adult, Middle Aged, Female, Male |
| الوصف: | Objective Dominant mutations in the three collagen VI genes cause Bethlem myopathy, a disorder characterized by proximal muscle weakness and commonly contractures of the fingers, wrists, and ankles. Although more than 20 different dominant mutations have been identified in Bethlem myopathy patients, the biosynthetic consequences of only a subset of these have been studied, and in many cases, the pathogenic mechanisms remain unknown. Methods We have screened fourteen Bethlem myopathy patients for collagen VI mutations and performed detailed analyses of collagen VI biosynthesis and intracellular and extracellular assembly. Results Collagen VI abnormalities were identified in eight patients. One patient produced around half the normal amount of alpha1(VI) messenger RNA and reduced amounts of collagen VI protein. Two patients had a previously reported mutation causing skipping of COL6A1 exon 14, and three patients had novel mutations leading to in-frame deletions toward the N-terminal end of the triple-helical domain. These mutations have different and complex effects on collagen VI intracellular and extracellular assembly. Two patients had single amino acid substitutions in the A-domains of COL6A2 and COL6A3. Collagen VI intracellular and extracellular assembly was normal in one of these patients. Interpretation The key to dissecting the pathogenic mechanisms of collagen VI mutations lies in detailed analysis of collagen VI biosynthesis and assembly. The majority of mutations result in secretion and deposition of structurally abnormal collagen VI. However, one A-domain mutation had no detectable effect on assembly, suggesting that it acts by compromising collagen VI interactions in the extracellular matrix of muscle. ; Naomi L. Baker, Matthias Mörgelin, Rishika A. Pace, Rachel A. Peat, Naomi E. Adams, R. J. McKinlay Gardner, Lewis P. Rowland, Geoffrey Miller, Peter De Jonghe, Berten Ceulemans, Mark C. Hannibal, Matthew Edwards, Elizabeth M. Thompson, Richard Jacobson, Ros C. M. Quinlivan, Salim Aftimos, Andrew J. ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0364-5134 1531-8249 |
| العلاقة: | Annals of Neurology, 2007; 62(4):390-405; http://hdl.handle.net/2440/44029Test |
| DOI: | 10.1002/ana.21213 |
| الإتاحة: | https://doi.org/10.1002/ana.21213Test http://hdl.handle.net/2440/44029Test |
| حقوق: | Copyright © 2007 American Neurological Association |
| رقم الانضمام: | edsbas.97F03902 |
| قاعدة البيانات: | BASE |
| تدمد: | 03645134 15318249 |
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| DOI: | 10.1002/ana.21213 |