Respiratory insufficiency in desminopathy patients caused by introduction of proline residues in desmin c-terminal alpha-helical segment
| العنوان: | Respiratory insufficiency in desminopathy patients caused by introduction of proline residues in desmin c-terminal alpha-helical segment |
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| المؤلفون: | Aleksey Shatunov, David Hilton-Jones, Waney Squier, James W. Nagle, Bertrand Goudeau, Patrick Vicart, Jan Blancato, Ayush Dagvadorj, Lev G. Goldfarb, Monique Simon-Casteras |
| المصدر: | Muscle and nerve. 27(6) |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | Adult, Male, Pathology, medicine.medical_specialty, Proline, Physiology, DNA Mutational Analysis, Molecular Sequence Data, Muscle Fibers, Skeletal, Intermediate Filaments, macromolecular substances, Biology, medicine.disease_cause, Protein Structure, Secondary, Cell Line, Desmin, Cellular and Molecular Neuroscience, Muscular Diseases, Physiology (medical), medicine, Respiratory muscle, Humans, Genetic Testing, Respiratory system, Intermediate filament, Myopathy, Aged, Mutation, Muscle Weakness, Base Sequence, Sequence Homology, Amino Acid, Respiratory disease, Muscle weakness, Middle Aged, medicine.disease, Respiratory Paralysis, Respiratory Muscles, Female, Neurology (clinical), medicine.symptom, Respiratory Insufficiency |
| الوصف: | Mutations in desmin gene have been identified in patients with cardiac and skeletal myopathy characterized by intracytoplasmic accumulation of desmin-reactive deposits and electron-dense granular aggregates. We characterized two new desminopathy families with unusual features of adult-onset, slowly progressive, diffuse skeletal myopathy and respiratory insufficiency. Progressive reduction of respiratory muscle strength became clinically detectable between the 3rd and the 8th years of illness and led to recurrent chest infections and death in one of the patients. Novel mutations, A357P and L370P, predicted to introduce proline residue into a highly conserved α-helical region of desmin, were identified. Proline is known to disrupt the α-helix. In addition, the A357P mutation distorts a unique stutter sequence that is considered to be critically important for proper filament assembly. Functional assessment in two cell-lines, one of which does and the other of which does not constitutively produce type III intermediate filaments, demonstrated the inability of mutant desmin carrying either the A357P or the L370P mutation to polymerize and form an intracellular filamentous network. The results of this study indicate that respiratory insufficiency is an intrinsic feature of disease associated with specific desmin mutations; in some patients, respiratory weakness may present as a dominant clinical manifestation and a major cause of disability and death. Muscle Nerve 27: 669–675, 2003 |
| اللغة: | English |
| تدمد: | 1097-4598 0148-639X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::234f19a1360ff1d1cce1e0fd4b863b68Test http://ora.ox.ac.uk/objects/uuid:b4eb305e-5da2-4ac2-90dd-68ad9e0306a3Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....234f19a1360ff1d1cce1e0fd4b863b68 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974598 0148639X |
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