1992 Fiscal Year Final Research Report Summary
Molecular genetic study on patients with various types of von Willebrand disease
| Project/Area Number |
02454273
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | NARA MEDICAL UNIVERSITY |
|---|
Principal Investigator |
FUKUI Hiromu NARA MEDICAL UNIVERSITY, PEDIATRICS, PROFESSOR, 医学部・小児科, 教授 (20075104)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Takuya NARA MEDICAL UNIVERSITY, PEDIATRICS, ASSISTANT, 医学部(小児科), 助手 (00192253)
NISHINO Masato NARA MEDICAL UNIVERSITY, PEDIATRICS, ASSISTANT PROFESSOR, 医学部(小児科), 講師 (60164571)
SHIMA Midori NARA MEDICAL UNIVERSITY, PEDIATRICS, ASSISTANT PROFESSOR, 医学部(小児科), 講師 (30162663)
TAKAHSHI Yukihiro NARA MEDICAL UNIVERSITY, NICU, ASSOCIATE PROFESSOR, 医学部(新生児病室), 助教授 (60142379)
FUJIMURA Yoshihiro NARA MEDICAL UNIVERSITY, TRANSFUSION, ASSOCIATE PROFESSOR, 医学部(輸血部), 助教授 (80118033)
|
|---|
| Project Period (FY) |
1990 – 1992
|
| Keywords | von Willebrand disease / von Willebrand factor / vWD TypeI / vWD TypeIIA / vWD TypeIIB / vWD TypeIIC / vWF gene / vWF subunit |
|---|
| Research Abstract |
We have investigated vWF gene lesions and functional domains of vWF-subunit in patients with various types of vWD.
1. Gene analysis: Taq I RFLPs patterns using 3.3Kb cDNA 3'end fragment were observed in 9 patients with vWD including 3 Type I, 4 IIA, 1 IIB and 1 IIC. No major delesions of vWF gene were observed in these cases.
A variable number tandem repeat(VNTR) within intron 40 of the vWF gene was investigated in patients with vWD. Seven of 11 cases were shown to be heterozygous for this vWF-VNTR.
A new variant vWD with defective binding to factor VIII showed a mutation from Arg(53) to trp. A patient with Type IIB vWD was found to have the Arg(54) to Cys substitution.
2. Analysis of functional domains of vWF: Factor VIII binding ability of vWF in several types of vWD was analyzed in a solid phase assay. Types IIA, IIB and IIC showed normal binding ability. However, a patient who was formally diagnosed as female hemophilia was shown to be unable to bind F. VIII.
We have shown that the purified two-chain Botorocetin binds to vWF from plasmas of patients with type IIA or IIB vWD and its interaction is indistinguishable from normal individuals.
The percentage of binding of vWF to human TypeIII fibrillar collagen was determined in plasm samples from various types of vWD. The levels of collagen binding were normal in TypeI, but decreased in TypesIIA, IIB and IIC.
|
