1997 Fiscal Year Final Research Report Summary
Research on the basic defect of carbohydrate-deficient glycoprotein syndrome
| Project/Area Number |
08670887
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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 | Tottori University |
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Principal Investigator |
OHNO Kousaku Tottori University, Department of Neurobiology, Professor, 医学部, 教授 (70112109)
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| Co-Investigator(Kenkyū-buntansha) |
HIGAKI Katsumi Tottori University, Department of Nerobiology, Lecturer, 医学部, 助手 (90294321)
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| Project Period (FY) |
1996 – 1997
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| Keywords | carbohydrate-deficient glycoprotein syndrome / disialotransferrion / asiolotransferrin / dehydrodolichol reductase |
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| Research Abstract |
The carbohydrtae-deficient glycoprotein (CDG) syndrome is newly recongized genetic disorder characterize by apppearance of serum asialo-and disialo-transferrin. We have previously reported that the sugar chain attached to transferrin in the patients is structurally normal and a defect in asparagine N-linked sugar chain in one or two of the possible glycosylation sites.
In this study we have analyzed metabolic pathways from precursors to lipid linked oligosaccharide. When CDG fibroblasts were loaded with [3H] glucosamine and analyzed lipid linked oligosaccharide intermediates, the intermediates in CDG fibroblasts were decreased without specific block. Then we have loaded [3H] mannose and analyzed lipid linked oligosaccharide intermediates. We could not find any metabokic block in this pathway. Finally we have loaded [3H] mevalonic acid and found a metabolic block in a step from dehydrodolicol to dolicol. We have concluded that appearance of glycoproteins lacking sugar chain may caused by a partial deficiency of dehydrodolicol reduction^<2)>.
Prenatal diagnosis of CDG syndrome using carbohydrate-deficient glycoprotein in cordblood has been reported to be impossible, because carbohydrate-deficient glycooproteins appear after birth. To detect abnormal processing of intracellular glycoprotein, we have studied lysosomal enzyme proteins in cultures CDG fibroblasts. Although we could not find any abnormally glycosylated enzyme proteins, we have found an increase in alpha chain of beta hexosaminidase protein, suggesting abnormal processing of hexosaminidase protein^<3)>.
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