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Immunological, Biological and Molecular Genetic Study on Prenatal Diagnosis of Hemophilia

Research Project

Project/Area Number 63480239
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionNara Medical University

Principal Investigator

YOSHIOKA Akira  Nara Medical University, Pediatrics, Associate Professor, 医学部・小児科, 助教授 (40106498)

Co-Investigator(Kenkyū-buntansha) KORESAWA Mitsuhiko  University of Tsukuba, Obst. & Gynecol, Assistant Professor, 医学部・臨床医学系・産婦人科, 講師 (60107703)
SHIMA Midori  Nara Medical University, Pediatrics, Assistant Professor, 医部部・小児科, 講師 (30162663)
NISHINO Masato  Nara Medical University, Pediatrics, Assistant Professor, 医学部・小児科, 講師 (60164571)
TANAKA Ichiro  Nara Medical University, Pediatrics, Assistant, 医学部・小児科, 助手 (00201616)
NISHIMURA Takuya  Nara Medical University, Pediatrics, Assistant, 医学部・小児科, 助手 (00192253)
Project Period (FY) 1988 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1990: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1989: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1988: ¥3,000,000 (Direct Cost: ¥3,000,000)
KeywordsHemophilia / Factor VIII / Factor IX / Carrier detection / Prenatal diagnosis / Fetal blood sampling / Chorionic villus sampling / Gene analysis / 血友病A / 血友病B / RFLP(restriction fragment length polymorphism) / 第IV因子 / CVS(chorionic villi sampling) / モノクローナル抗体 / RFLP(restriction fragment length polyworphism)
Research Abstract

1) Carrier detection
(1) Clotting and immunochemical diagnosis ; It was confirmed that FVIII : C, FVIII : Ag and vWF : Ag were useful for carrier detection of hemophilia A, and that FIX : C, FIX : Ag and ox brain PT were useful for that of hemophilia B.
(2) Restriction fragment length polymorphism (RFLP) ; BcII/intron 18 (frequency 27-30%) and XbaI/intron22 (67%) polymorphism in the FVIII locus were useful for carrier detection of hemophilia A. SstI/pX58dIIIc (frequency 40%) and TaqI/pX45h (30%) polymorphism closely to the FIX gene were useful for hat of hemophilia B.
2) Sex diagnosis
(1) First trimester diagnosis by chorionic villus sampling (CVS) Sex diagnosis was achieved at 9-11 weeks of gestation by the use of RFLP of EcoRI/DYZ1 (Y-chromosome specific gene probe).
(2) Second trimester diagnosis by amniocentesis ; Sex diagnosis was also performed by chromosome analysis of amniotic fluid cells.
(3) Prenatal diagnosis of hemophilia A by fetal blood sampling
10 female fetuses out of 33 fetus … More es went to term uneventfully. For accurate mid-trimester prenatal diagnosis, fetal liver or cord blood from 23 male fetuses at 50% risk was sampled using a needle guided by ultrasound. FVIII : C and FVIII : Ag in the fetal plasma were assayed. Then, 6 affected fetuse were artificially aborted and the remaining 17 fetuses went to term.
4) Prenatal diagnosis of hemophilia A by CVS
For accurate first-trimester prenatal diagnosis CVS from 9 fetuses at 25% risk was performed. According to RFLP analysis, 3 cases of 6 female fetuses were carrier and 3 cases were not carrier. Both of them went to term. Two out of the remaining 3 male fetuses were found to be affected and aborted. One was not affected and went to term.
5) Prenatal diagnosis of hemophilia B
Eleven fetuses of 6 carriers were investigated. Four were female and went to term. Three of 7 male fetuses were aborted without prenatal diagnosis. Two of the 4 male fetuses were diagnosed to be affected and aborted, whereas the remaining 2 were not affected and went to term. One woman gave birth to a normal male, however, the other gave birth to hemophilia B patient. This was an only one case of wrong diagnosis. Less

Report

(4 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • 1988 Annual Research Report
  • Research Products

    (59 results)

All Other

All Publications (59 results)

  • [Publications] A.Yoshioka et al.: "Prenatal dingnosis of haemophilia BM" Japanese Journal of Human Genetics. 33. 395-400 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] A.Yoshioka et al.: "First trimester prenatal diagnosis of haemophilia A using factor VIII gene probe" Japanese Journal of Human Genetics. 34. 135-141 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 吉岡 章他: "血友病の出生前診断" 血液と脈管. 20. 368-373 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 西村 拓也他: "血友病出生前診断におけるY染色体特異DNAプロ-ブの有用性" 臨床遺伝研究. 11. 1-9 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 是澤 光彦他: "胎児採血の適応と方法" 産婦人科治療. 58. 546-548 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 吉岡 章: "遺伝相談におけるインフォ-ムドコンセント ー血友病遺伝相談を中心にー" ペリネイタルケア. 9. 869-874 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 吉岡 章: "小児科の進歩9 「血友病の遺伝子相談」" 診断と治療社, 81 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 吉岡 章: "Annual Review 血液1990 V.5.異常第IX因子" 中外医学社, 9/216 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] H. Nakai et al.: "Production of factor VIII deficient plasma by immunodepletion using monoclinal antibodies to vWF and to factor VIII, and its application. (japanese)" Clinical Pathology. 36(4). 475-480 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] A. Yoshioka: "Symposium on activation of regional genetic service. II. Training and maintenance of manpower. Role of local administration. (japanese)" Med. Gent. Res. 9(3.4). 120-130 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] M. Shimna et al.: "Factor VIII polypeptide specificity of momnoclical anti-factor VIII antibodies." Br. J. Haematol. 70. 63-69 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] M. Sugimoto et al.: "Blood clotting factor IX Niigata : Substitution of alanine-390 by valine in the catalytic domain." J. Biochemistry. 104. 878-880 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] A. Yoshioka et al.: "Prenatal diagnosis of haemophilia BM." Jpn. J. Human Genet. 33. 395-400 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] S. Mikami et al.: "A deletion involving intron 13 and exon 14 of factor VIII gene in a haemophiliac with anti-factor VIII antibody." Jpn. J. Human Genet.33. 401-407 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] S. Mikami et al.: "Nonsense mutation in factor VIII gene of a severe haemophiliac patient with anti-factor VIII antibody." Jpn. J. Human Genet. 33. 409-415 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T. Nishimura: "Restriction fragment length polymorphism in hemophilia B families. I. Analysis of polymorphism in factor IX gene in normal Asians. (Japanese)" J. Nara Med. Ass.39(4). 531-541 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T. Nishimura: "Restriction fragment length polymorphism in hamophilia B families. II. Carrier detection of hemophilia B using probes to DNA segments closely linked to factor IX gene. (Japanese)" J. Nara Med. Ass.39(5). 585-590 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] A. Yoshioka: "Hemophilia and von Willebrand Disease. (Japanese)" Medical Practice. 5(10). 1750-1750 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T. Sakai et al.: "Blood clotting factor IX Kashihara : Amino acid substitution of valine-182 by phenylalanine." J. Biochemistry. 105. 756-759 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] I. Tanaka et al.: " Two cases of hemophilia A in girs. (Japanese)" Jpn. J. Pediatr. Hematol.3. 173-178 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] A. Yoshioka et al.: "First trimester prenatal diagnosis diagnosis of haemophilia A using factor VIII gene probe." Jpn. J. Human Genet.34. 135-141 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] M. Sugimoto et al.: "Factor IX Kawachinagano : impaired function of the Gladomain caused by attached polpeptide region due to substitution of arginine by glutamine at position -4." Br. J. Haematol.72. 216-221 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] M. Shima et al.: "An arginine to cystiene amino acid substitution at a critical thrombin cleavage site in a dysfunctional factor VIII molecule." Blood. 74(5). 1612-1617 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T. Nishimura et al.: "Application of Y-chromosome specific DNA probe to antenatal diagnosis of hemophilia. (Japanese)" Med. Genet. Res.11(1.2). 1-9 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T. Nishimura et al.: "Mode of inheritance and gene analysis of hemophilia. (Japanese)" Sogorinsho. 38(6). 1773-1780 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] A. Yoshioka.: "A new view of genetic counseling in hemophilia. (Japanese)" Med. Genet. Res.10(3.4). 90-100 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] M. Koresawa et al.: "Purpose and methods of fetal blood sampling. (Japanese)" Obst. & Glnecl.58. 546-548 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] A. Yoshioka et al.: "Prenatal diagnosis of hemophilia. (Japanese)" Blood & Vessel. 20(4). 368-373 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] A. Yoshioka: "Recent advances in hemophilia research -Gene analysis and its application-(Japanese)" Bone. Joint & Ligament. 3(5). 431-442 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] A. Yoshioka et al.: "Congenital factor IX abnormalities. (Japanese)" Clinical Pathology sppl.86. 63-72 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] F. Giannelli et al.: "Haemophilia B database of point mutations and short additions and deletions." Nucleic Acid Res.18(14). 4053-4059 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] M. Shima: "Molecular defects of factor VIII. (Japanese)" Jpn. J. Thromb. Hemost.1(4). 285-296 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T. Nishimura et al.: "Missense mutations in Factor IX Kashihara and Factor IX Niigata." Acta Haematol. Jpn.53(6). 1030-1035 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] A. Yoshioka: "Carrier detection of hemophilia. (Japanese)" Gendaiiryou. 22 (suppl. 11). 182-187 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] A. Yoshioka: "Informed consent in genetic counseling -Genetic counseling of hemophilia- (Japanese)" Perinatal Care. 9. 869-874 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] A. Yoshioka: "Development of prenatal diagnosis of hemophilia. (Japanese)" Nihon-iji-shinpou. No. 3429. 171 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] A. Yoshioka: "Genetic analysis of hemophilia. (Japanese)" Igaku-kensa. 40(1). 100-194 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] I. Tanaka et al.: "Female hemophilia. (Japanese)" Shouni-naika. 23(2). 189-194 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 吉岡 章他6名: "凝固IX因子異常症" 臨床病理(臨時増刊). 特集第86号. 63-72 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Nishimura et al.他10名: "Missense mutations in Factor IX Kashihara and Factor IX Niigata" Acta Haematologica Japonica. 53. 1030-1035 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 吉岡 章: "血友病出生前診断の発展" 日本医事新報. 3429. 171-171 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 吉岡 章: "血友病保因者の診断" 現代医療. 22増II. 182-186 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 吉岡 章: "血友病研究の最近の進歩 遺伝子解析とその応用" 骨・関節・靭帯. 3. 431-442 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 吉岡 章: "遺伝相談におけるインフォ-ムドコンセントー血友病遺伝相談を中心にー" ペリネイタルケア. 9. 869-874 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 吉岡 章: "Annual Review 血液1990 V.5.異常第IX因子" 中外医学社, 9/216 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 吉岡 章: "血液疾患診療マニュアル§5.3.血友病と類縁疾患" 中外医学社, 30/366 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] 吉岡章: "血友病遺伝相談の新しい展望" 臨床遺伝研究. 10. 90-100 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] A.Yoshioka et al.: "First trimester prenatal diagnosis of haemophika A using factor VIII gene probe" Jpn.J.Human Genet.34. 135-141 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 吉岡章 他: "血友病の出生前診断" 血液と脈管. 20. 368-373 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 西村拓也 他: "血友病の遺伝形式と遺伝子診断" 綜合臨床. 38. 1773-1780 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 西村拓也 他: "血友病出生前診断におけるY染色体特異DNAプロ-ブの有用性" 臨床遺伝研究. 11. 1-9 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 是澤光彦 他: "胎児採血の適応と方法" 産婦人科治療. 58. 546-548 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 吉岡章: "小児科の進歩9「血友病の遺伝相談」" 診断と治療社, 67-74 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] A.YOSHIOKA,et al: Jpn.J.Human Genet. 33. 395-400 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] M.NISHINO/T.NISHIMURA,et al: Jpn.J.Human Genet. 32. 237-245 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] 西村拓也: 奈良医学雑誌. 39. 531-541 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 西村拓也: 奈良医学雑誌. 39. 585-590 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 吉岡章: 臨床病理. 臨増73号. 63-73 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] 是澤光彦 他: 日本産婦人科学会雑誌. 39. 395-399 (1987)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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