Molecular genetic study of succinate dehydrogenase deficiency
| Project/Area Number |
09670684
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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 | National Institute of Neuroscience National Center of Neurology and Psychiatry (NCNP) |
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Principal Investigator |
GOTO Yu-ichi National Institute of Neuroscience, Department of Ultrastructural Reseach, Head, 神経研究所・微細構造研究部, 室長 (20225668)
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| Co-Investigator(Kenkyū-buntansha) |
NONAKA Ikuya National Institute of Neuroscience, Department of Ultrastructural Reseach, Direc, 神経センター・神経研究所・微細構造研究部, 部長 (80040210)
西野 一三 国立精神, 神経センター・神経研究所・微細構造研究部, 流動研究員
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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: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | succinate dehydrogenase / flavoprotein / complex II / molecular genetics / inborn error of metabolism / mitochondrial disease / フラビンタンパク / 鉄-イオウ蛋白 / cDNA / 電子伝達系 |
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| Research Abstract |
We have done the molecular genetic study of 5 patients in 4 families with succinate dehydrogenase deficiency in skeletal muscle. Succinate dehydrogenase is a part of complex II in electron transfer system and its core activity is located in the flavoprotein (Fp) subunit. We examined all cDNA of complex II including the Fp subunit in all 5 patients. In result, we found the compound heterozygous point muations only in the 2-year-old boy who had myopathy without central nervous system symptoms. One was a C-to-T mutation in nucleotide number 1181 resulting in Thr386Ile, the other was a G deletion in nucleotide number 1756 resulting in alterlation from Arg589 and premature stop at 54-amino-acid downstream. These two mutations were present in his genomic DNA, and also in his parents' genomic DNAs, respectively. As the Fp gene is known to be mapped at two chromosomal loci, we again found at least 4 alleles using PCR amplification of the regions near the mutation sites. Moreover, immunohistochemical analysis using Ascaris anti-Fp antibody showed positive stain in only type 2 fibers, which strongly suggested the presence of isoforms of the Fp subunit in skeletal muscle. In contrast, we tried to find the other causes for the patients without Fp gene mutation, but there was no abnormality in the frataxin gene, which is responsible for Friedreich's ataxia, or in the superoxide dismutase 2 gene, whose disruptioninduced severe deficiency of succinate dehydrogenase in mice. In future, we need to confirm the isoforms of the Fp subunit and to study the biological effects of succinate dehydrogenase deficiency at cellularlevel.
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Report
(3 results)
Research Products
(13 results)
