| Project/Area Number |
17590857
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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 | Tohoku University |
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Principal Investigator |
AOKI Masashi Tohoku University, Hospital, Research Associate, 病院, 助手 (70302148)
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| Co-Investigator(Kenkyū-buntansha) |
ITOYAMA Yasuto Tohoku University, Graduate School of medicine, Professor, 大学院医学系研究科, 教授 (30136428)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | dysferlin / Distal myopathy / gene / Miyoshi myopathy / muscular dystrophy |
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| Research Abstract |
Muscular dystrophies with an autosomal recessive mode of inheritance constitute a genetically heterogeneous group of disorders. Distal myopathies (also designated distal muscular dystrophies) are by definition disorders with weakness and atrophy predominantly in the distal muscles. Miyoshi myopathy (MM) is an autosomal recessive distal muscular dystrophy characterized by mid-to late childhood or early adulthood onset, with preferential involvement of the calf muscles and highly elevated levels of the enzyme serum creatine kinase. MM was first described by Miyoshi in Japan. The main locus for MM was mapped to chromosome 2p13. However the MM pedigrees showed non-linkage to chromosome 2p, indicating there is genetic heterogeneity in this disease.
Mutations in the dysferlin gene cause both MM and limb girdle muscular dystrophy 2B (LGMD2B). However, dysferlinopathy exhibits marked heterogeneity in the initial distribution of muscle involvement at the onset of the disease. Some additional factors distinct from dysferlin are considered to be involved in the pathomechanism.
We describe a Japanese patient with dysferlinopathy who exhibited distal anterior compartment myopathy (DACM) with early contractures of the ankle, whose pedigree included patients with two other types of dysferlinopathy. Gene analysis confirmed that all the patients in the family shared the same homozygous dysferlin 4870delT mutation. The existence of three phenotypes of dysferlinopathy in one pedigree is reported for the first time, indicating the involvement of molecules other than dysferlin in the pathomechanism.
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