| Project/Area Number |
12670739
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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 |
Pediatrics
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| Research Institution | Gifu University |
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Principal Investigator |
SUZUKI Yasuyuki Gifu University School of Medicine, Professor, 医学部, 助教授 (00163014)
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| Co-Investigator(Kenkyū-buntansha) |
FUKAO Toshiyuki Gifu university Hospital, Assistant professor, 医学部・附属病院, 講師 (70260578)
SHIMOZAWA Nobuyuki Gifu University School of Medicine, Associate professor, 医学部, 助教授 (00240797)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Dicarboxylic acid / ABC protein / Peroxisome biogenesis disorder / Acyl-CoA oxidase / アシルーCOAオキシダーゼ / ABC蛋白 / ペルオキシソーム / 先天代謝異常症 |
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| Research Abstract |
Abnormal excretion of dicarboxylic acids in urine is found in patients with mitochondrial fatty acid disorders, peroxisomal disorders and others. This biochemical abnormality is considered to relate to developmental disorders. Recently, a peroxisomal integral membrane protein PMP70 which is a member of ATP binding cassette protein (ABC protein) superfamily, was found to be a transporter of long chain dicarboxylic acids, and these dicarboxylic acids are considered to be degraded in peroxisomes. We investigated pathogenesis of inborn errors of dicarboxylic acid and defects of ABC proteins.
(1) PEX1p, a member of ABC protein and a pathogenic protein of Zellweger syndrome (peroxisome biogenesis disorders) , was found to interact with PEX6p, an another ABC protein and a pathogenic protein of Zellweger syndrome.
(2) PEX6p was found to be a pathogenic protein of complementation group 6 of Zellweger syndrome.
(3) We identified 3 patients with peroxisomal acyl-CoA oxidase deficiency which was characterized by accumulation of very-long chain fatty acids and dicarboxylic aciduria. Characteristic brain MRI findings were similar to those of cerebello-brainstem type of adrenoleukodystrophy.
(4) We reported the first family cases of PEX6p deficiency. Parents manifested visual disturbance which was similar to Usher syndrome, and the child suffered severe psychomotor retardation typical for peroxisome biogenesis disorders.
(5) Natural history of Japanese children with adrenoleukodystrophy which is caused by a defect in ALD protein, an ABC protein, was clarified.
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