1993 Fiscal Year Final Research Report Summary
Clinical application of polymorphisms in coagulation factor XIII A subunit gene and molecular analysis of the patients with its deficiency.
| Project/Area Number |
04670392
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
OKAMURA Takashi KYUSHU UNIVERSITY, FACULTY OF MEDICINE, ASSITANT PROFESSOR, 医学部, 助手 (30136436)
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| Co-Investigator(Kenkyū-buntansha) |
TESHIMA Takanori KYUSHU UNIVERSITY, FACULTY OF MEDICINE, SENIOR RESIDENT, 医学部, 医員
MURAKAWA Masahiro KYUSHU UNIVERSITY, FACULTY OF MEDICINE, SENIOR RESIDENT, 医学部, 医員
KAMURA Takumi KYUSHU UNIVERSITY, FACULTY OF MEDICINE, SENIOR RESIDENT, 医学部, 医員
HARADA Mine KYUSHU UNIVERSITY, FACULTY OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (00019621)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Coagulation factor XIII / Congenital bleeding disorder / Gene analysis / Congental factor XIII deficiency / Gene polymorphism |
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| Research Abstract |
We newly found two RFLP sites(A and B)which digested by restriction enzyme Pvu II in coagultion factor XIII A subunit gene. By Southern blot analysis using factor XIII A subunit cDNA as a probe, A site present in Intron D formed 7.4 and 7.0kb band, and B site present in Intron I made 6.4 and 6.0kb band. In normal Japanese population, their allele frequencies were 0.66/0.34 and 0.46/0/56, respectively. In clinically, these RFLPs may be useful for a confirmation of the engraftment following allogenic bone marrow transplantation and detection of the carrier state of factor XIII A subunit deficiency.
In two patients with factor XIII A subunit deficiency, gene analyzes were performed. By -PCR method, the exons(II-XV) and adjacent introns were amplified and sequenced. Factor XIII A subunit mRNA from peripheral monocytes were also sequenced. In first case, these sequencing revealed a delection of the dinucleotide AG at the position of 212 and 213 in cDNA number, which correspond to 5' end of Exon III.This deletion appeared to cause a frameshift mutation making a new stop codon shortly thereafter, and leading to a deficiency of plasma factor XIII A subunit. In second case, point mutation (866G->A)in Exon IV was found, and made a substitution of 260 Arg to His. In 50 normal subjects, this point mutation could not be identified. Therefore, this mutation might be associated with the deficiency of factor XIII A subunit. Further analysis should be needed to elucidate why the point mutation causes the deficiency.
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