| Project/Area Number |
06454311
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | The Tokyo Metropolitan Institute of Medical Science |
|---|
Principal Investigator |
SUZUKI Yoshiyuki Vice-Director, The Tokyo Metropolitan Institute of Medical Scince, 副所長 (90010389)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OSHIMA Akihiro Inverstigator, Department of Clinical Genetics, The Tokyo Metropolitan Institute, 臨床遺伝学研究部門, 研究員 (20203763)
ITOH Kohji Investigator, Department of Clinical Genetics, The Tokyo Metropolitan Institute, 臨床遺伝学研究部門, 研究員 (00184656)
SAKURABA Hitoshi Head, Department of Clinical Genettics, The Tokyo Metropolitan Institute of Medi, 臨床遺伝学研究部門, 研究員 (60114493)
OHNO Kousaku Professor, Department of Neurobiology, Tottori University, 医学部, 教授 (70112109)
|
|---|
| Project Period (FY) |
1994 – 1995
|
| Project Status |
Completed (Fiscal Year 1995)
|
| Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1995: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1994: ¥4,100,000 (Direct Cost: ¥4,100,000)
|
|---|
| Keywords | CDG syndrome / alpha-fucosidase / beta-hexosaminidase / transferrin / antithrombin / phosphomannomutase / α-フコシダーゼ / オリゴ糖 / 糖蛋白質 / 先天性代謝異常 |
|---|
| Research Abstract |
CDG syndrome is a recently identified hereditary disease with unique neurological and general somatic manifestations, and its etiology and pathogenesis are have been unknown up till recently. We tried to analyze molecular abnormalities in somatic cells from patients with this disease. Among several lysosomal enzymes, beta-hexosaminidase and alpha-fucosidase showed high catalytic activities in serum. The electrofocusing pattern of the latter revealed an increase of protein bands moving more toward the anode, indicating an increase of sialic acid-containing glyco-protein molecules. Serum transferrin and antithrombin contained abnormal molecules of small size detected by immunoblotting. The mature alpha-subunit of beta-hexosaminidase was increased in cultured fibroblasts, but normal extracellularly. In these cells, phosphomannomutase activity was extremely low in two patients. This abnormality probably induces a decrease of intra-cellular mannose 1-phosphate and GDP-mannose, resulting in insufficient glycosylation of glycoprotein molecules.
|
