| 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 (1998) The University of Tokushima, Medical School Hospital, Assistant Professor, 医学部附属病院, 講師 (60274198)
川井 尚臣 (1997) 徳島大学, 医学部, 助教授 (00035461)
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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)
三ツ井 貴夫 徳島大学, 分子酵素学研究センター, 助手 (80294726)
西田 義彦 徳島大学, 医学部・附属病院, 講師 (30198478)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | limb-girdle muscular dystrophy / LGMD2A / calpain 3 / autosomal recessifve / mutation / Z band / 肢体型筋ジストロフィー症 / ミスセンス変異 / Frame shift / 筋ジストロフィー / 悪性肢帯型 / サルコグリカン / 遺伝子 / サルコグリカノパチー |
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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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