| Project/Area Number |
25461537
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Yamagata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NUMAKURA Chikahiko 山形大学, 医学部, 講師 (00400549)
ABE Akiko 山形大学, 医学部, 非常勤講師 (10536949)
TAKAHASHI Nobuya 山形大学, 医学部, 医員 (20536958)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 遺伝性ニューロパチー / Charcot-Marie-Tooth病 / 軸索型 / 混合型 / チトクロームオキシダーゼ / COX6A1 / cytochrome c oxidase / respiratory complex IV / 軸索 / 連鎖解析 / 呼吸鎖複合体 / 次世代シークエンサー / エクソーム解析 |
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| Outline of Final Research Achievements |
Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy, but causing gene mutation is not unknown in half of the patients. We studied two consanguineous families with CMT (axonal and mixed phenotypes) by SNP array and whole-genome sequencing analyses and finally detected a disease-specific 5 bp deletion (c.247-10_247-6delCACTC) in a splicing element (pyrimidine tract) of intron 2 adjacent to the third exon of cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1). Functional analysis showed that expression of COX6A1 in peripheral white blood cells from the affected individuals and COX activity in their EB-virus-transformed lymphoblastoid cell lines were significantly reduced. In addition, Cox6a1-null mice showed significantly reduced COX activity and neurogenic muscular atrophy leading to a difficulty in walking. Those data indicated that COX6A1 mutation causes the autosomal-recessive axonal or mixed CMT.
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