Brody disease: insights into biochemical features of SERCA1 and identification of a novel mutation
| Autor: | Giuliano Tomelleri, Anna Russignan, Marcella Neri, Toin H. van Kuppevelt, Paola Tonin, Matteo Marini, Consuelo Poli, Gaetano Vattemi, Arie Oosterhof, Paola Rimessi, Valeria Guglielmi, Alessandra Ferlini, Francesca Gualandi |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Pathology Biopsy Myopathy DNA Mutational Analysis Muscle Fibers Skeletal Sarcoplasm 2-Dimensional gel electrophoresis ATP2A1 gene Brody disease Sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 1 0302 clinical medicine Muscle Hypertonia 0303 health sciences Exercise Tolerance medicine.diagnostic_test Genetic disorder General Medicine Sarcoplasmic/endoplasmic reticulum Ca Middle Aged Sarcoplasmic Reticulum Phenotype Muscle relaxation medicine.anatomical_structure Neurology Female medicine.symptom 2+ ATPase 1 Genetic Markers medicine.medical_specialty Genotype Down-Regulation Biology Sarcoplasmic Reticulum Calcium-Transporting ATPases Pathology and Forensic Medicine NO Young Adult 03 medical and health sciences Cellular and Molecular Neuroscience Muscular Diseases Internal medicine medicine Humans Genetic Predisposition to Disease Calcium Signaling Muscle Skeletal 030304 developmental biology Muscle biopsy Endoplasmic reticulum Skeletal muscle medicine.disease Tissue engineering and pathology [NCMLS 3] Enzyme Activation Microscopy Electron Endocrinology Mutation Neurology (clinical) 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuropathology and Experimental Neurology, 69, 246-52 Journal of Neuropathology and Experimental Neurology, 69, 3, pp. 246-52 |
| ISSN: | 0022-3069 |
| DOI: | 10.1097/nen.0b013e3181d0f7d5 |
| Popis: | Contains fulltext : 88384.pdf (Publisher’s version ) (Closed access) Brody disease is an inherited disorder of skeletal muscle function characterized by increasing impairment of relaxation during exercise. The autosomal recessive form can be caused by mutations in the ATP2A1 gene, which encodes for the sarcoplasmic/endoplasmic reticulum Ca-ATPase 1 (SERCA1) protein. We studied 2 siblings affected by Brody disease. The patients complained of exercise-induced delay of muscle relaxation and stiffness since childhood and had gene analysis of ATP2A1. Morphologic and biochemical studies were performed on a muscle biopsy from 1 patient. The biopsy showed fiber size variation and increased numbers of fibers with internal nuclei. Ultrastructural examination revealed dilatation of lateral cisternae and proliferation of tubular elements of the sarcoplasmic reticulum. By immunohistochemistry, SERCA1 was expressed in a normal pattern, but sarcoplasmic reticulum Ca-ATPase activity was significantly reduced. Immunoblotting after high-resolution 2-dimensional gel electrophoresis showed a significant difference in the amount of SERCA1 protein between the patient and controls. Both patients were found to have 2 previously unreported in-frame deletions in ATP2A1. Because SERCA1 protein has specific biochemical characteristics in our patient, these results underline the importance of a pathologic and biochemical analyses for the diagnosis. In addition, we describe 2 novel mutations in the ATP2A1 gene. 01 maart 2010 |
| Databáze: | OpenAIRE |
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