1998 Fiscal Year Final Research Report Summary
Molecular genetic analysis and establishment of the genetic diagnosis of autosomal recessive malignant limb-girdle muscular dystrophy.
| Project/Area Number |
09670658
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
WAKAMATSU Nobuaki The University of Tokushima, Medical School Hospital, Assistant Professor, 医学部附属病院, 講師 (60274198)
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| Co-Investigator(Kenkyū-buntansha) |
HUJIWARA Souichirou The University of Tokushima, Medical School Hospital, Medical Staff, 医学部附属病院, 医員(臨床)
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| Project Period (FY) |
1997 – 1998
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| Keywords | limb-girdle muscular dystrophy / LGMD2A / calpain 3 / autosomal recessifve / mutation / Z band |
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| Research Abstract |
Autosomal recessive malignant limb-girdle muscular dystrophy is a clinical entity established by Dr. Miyoshi et al. in 1966. The patients show the muscular atrophy in the shoulder, pelvic girdles, and proximal limb muscles from childhood. Recently, disease causing genes of this disease, sarcoglycans (alpha, beta, gamma) and thiol proteinase ; calpain 3 were identified. We report on the clinical, pathological, and genetic analyses of seven patients (six men, one women) with autosomal recessive limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The mean age of onset was 9.7*3.1 years (mean*SD), and loss of ambulance occurred at 38.5*2.1 years. Muscular atrophy was predominant in the pelvic, shoulder girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes with patchy destruction of the myofibrillar Z, I, and A bands. In two families, an identical G to C mutation at position 1080th in the calpain 3 gene was identified. This mutation results in a W360R substitution in the proteolytic site of calpain 3. A frameshift mutation (1796 insA) which results in a deletion of the Ca^<2+> binding domain was also found in the third family. These results suggest that LGMD2A is caused by a deficiency of the calpain 3 protein results in the activation of proteolytic activities of proteases to the myofibrils or muscle fibers. In collaboration with Third Department of Internal Medicine, Kagoshima University, we also investigated the patients with severe childhood autosomal recessive muscular dystrophy with alpha-sarcoglycan or gamma -sarcoglycan deficiency.
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