Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1994 Nov 11;22(22):4851–4868. doi: 10.1093/nar/22.22.4851

Haemophilia A: database of nucleotide substitutions, deletions, insertions and rearrangements of the factor VIII gene, second edition.

E G Tuddenham 1, R Schwaab 1, J Seehafer 1, D S Millar 1, J Gitschier 1, M Higuchi 1, S Bidichandani 1, J M Connor 1, L W Hoyer 1, A Yoshioka 1
PMCID: PMC308545  PMID: 7984443

Abstract

A large number of different mutations in the factor VIII (F8) gene have been identified as a cause of haemophilia A. This compilation lists known single base-pair substitutions, deletions and insertions in the F8 gene and reviews the status of the inversional events which account for a substantial proportion of mutations causing severe haemophilia A.

Full text

PDF
4851

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Acquila M., Caprino D., Pecorara M., Baudo F., Morfini M., Mori P. G. Two novel mutations at 373 codon of FVIII gene detected by DGGE. Thromb Haemost. 1993 Apr 1;69(4):392–393. [PubMed] [Google Scholar]
  2. Aly A. M., Higuchi M., Kasper C. K., Kazazian H. H., Jr, Antonarakis S. E., Hoyer L. W. Hemophilia A due to mutations that create new N-glycosylation sites. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4933–4937. doi: 10.1073/pnas.89.11.4933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Antonarakis S. E., Waber P. G., Kittur S. D., Patel A. S., Kazazian H. H., Jr, Mellis M. A., Counts R. B., Stamatoyannopoulos G., Bowie E. J., Fass D. N. Hemophilia A. Detection of molecular defects and of carriers by DNA analysis. N Engl J Med. 1985 Oct 3;313(14):842–848. doi: 10.1056/NEJM198510033131402. [DOI] [PubMed] [Google Scholar]
  4. Arai M., Higuchi M., Antonarakis S. E., Kazazian H. H., Jr, Phillips J. A., 3rd, Janco R. L., Hoyer L. W. Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A. Blood. 1990 Jan 15;75(2):384–389. [PubMed] [Google Scholar]
  5. Arai M., Inaba H., Higuchi M., Antonarakis S. E., Kazazian H. H., Jr, Fujimaki M., Hoyer L. W. Direct characterization of factor VIII in plasma: detection of a mutation altering a thrombin cleavage site (arginine-372----histidine). Proc Natl Acad Sci U S A. 1989 Jun;86(11):4277–4281. doi: 10.1073/pnas.86.11.4277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bardoni B., Sampietro M., Romano M., Crapanzano M., Mannucci P. M., Camerino G. Characterization of a partial deletion of the factor VIII gene in a haemophiliac with inhibitor. Hum Genet. 1988 May;79(1):86–88. doi: 10.1007/BF00291718. [DOI] [PubMed] [Google Scholar]
  7. Berg L. P., Varon D., Martinowitz U., Wieland K., Kakkar V. V., Cooper D. N. Combined factor VIII/factor XI deficiency may cause intra-familial clinical variability in haemophilia A among Ashkenazi Jews. Blood Coagul Fibrinolysis. 1994 Feb;5(1):59–62. doi: 10.1097/00001721-199402000-00009. [DOI] [PubMed] [Google Scholar]
  8. Bernardi F., Legnani C., Volinia S., Patracchini P., Rodorigo G., DeRosa V., Marchetti G. A HindIII RFLP and a gene lesion in the coagulation factor VIII gene. Hum Genet. 1988 Apr;78(4):359–362. doi: 10.1007/BF00291736. [DOI] [PubMed] [Google Scholar]
  9. Bernardi F., Volinia S., Patracchini P., Gemmati D., Boninsegna S., Schwienbacher C., Marchetti G. A recurrent missense mutation (Arg----Gln) and a partial deletion in factor VIII gene causing severe haemophilia A. Br J Haematol. 1989 Feb;71(2):271–276. doi: 10.1111/j.1365-2141.1989.tb04266.x. [DOI] [PubMed] [Google Scholar]
  10. Bidichandani S. I., Shiach C. R., Lanyon W. G., Connor J. M. A novel splice donor mutation affecting position +3 in intron 6 of the factor VIII gene. Hum Mol Genet. 1994 Apr;3(4):651–653. doi: 10.1093/hmg/3.4.651. [DOI] [PubMed] [Google Scholar]
  11. Bröcker-Vriends A. H., Bakker E., Kanhai H. H., van Ommen G. J., Reitsma P. H., van de Kamp J. J., Briët E. The contribution of DNA analysis to carrier detection and prenatal diagnosis of hemophilia A and B. Ann Hematol. 1992 Jan;64(1):2–11. doi: 10.1007/BF01811464. [DOI] [PubMed] [Google Scholar]
  12. Bröcker-Vriends A. H., Briët E., Dreesen J. C., Bakker B., Reitsma P., Pannekoek H., van de Kamp J. J., Pearson P. L. Somatic origin of inherited haemophilia A. Hum Genet. 1990 Aug;85(3):288–292. doi: 10.1007/BF00206748. [DOI] [PubMed] [Google Scholar]
  13. Casula L., Murru S., Pecorara M., Ristaldi M. S., Restagno G., Mancuso G., Morfini M., De Biasi R., Baudo F., Carbonara A. Recurrent mutations and three novel rearrangements in the factor VIII gene of hemophilia A patients of Italian descent. Blood. 1990 Feb 1;75(3):662–670. [PubMed] [Google Scholar]
  14. Casula L., Murru S., Pecorara M., Ristaldi M. S., Restagno G., Mancuso G., Morfini M., De Biasi R., Baudo F., Carbonara A. Recurrent mutations and three novel rearrangements in the factor VIII gene of hemophilia A patients of Italian descent. Blood. 1990 Feb 1;75(3):662–670. [PubMed] [Google Scholar]
  15. Chan V., Chan T. K., Tong T. M., Todd D. A novel missense mutation in exon 4 of the factor VIII:C gene resulting in moderately severe hemophilia A. Blood. 1989 Dec;74(8):2688–2691. [PubMed] [Google Scholar]
  16. Collins P. W., Jenkins P. V., Goldman E., Lee C. A., Pasi K. J. Intron 22 inversions and haemophilia. Lancet. 1994 Mar 26;343(8900):791–791. [PubMed] [Google Scholar]
  17. Cotton R. G., Rodrigues N. R., Campbell R. D. Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4397–4401. doi: 10.1073/pnas.85.12.4397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Cutting G. R., Antonarakis S. E., Youssoufian H., Kazazian H. H., Jr Accuracy and limitations of pulsed field gel electrophoresis in sizing partial deletions of the factor VIII gene. Mol Biol Med. 1988 Dec;5(3):173–184. [PubMed] [Google Scholar]
  19. David D., Moreira I., Lalloz M. R., Rosa H. A., Schwaab R., Morais S., Diniz M. J., de Deus G., Campos M., Lavinha J. Analysis of the essential sequences of the factor VIII gene in twelve haemophilia A patients by single-stranded conformation polymorphism. Blood Coagul Fibrinolysis. 1994 Apr;5(2):257–264. doi: 10.1097/00001721-199404000-00016. [DOI] [PubMed] [Google Scholar]
  20. Diamond C., Kogan S., Levinson B., Gitschier J. Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A. Hum Mutat. 1992;1(3):248–257. doi: 10.1002/humu.1380010312. [DOI] [PubMed] [Google Scholar]
  21. Dombroski B. A., Mathias S. L., Nanthakumar E., Scott A. F., Kazazian H. H., Jr Isolation of an active human transposable element. Science. 1991 Dec 20;254(5039):1805–1808. doi: 10.1126/science.1662412. [DOI] [PubMed] [Google Scholar]
  22. Economou E. P., Kazazian H. H., Jr, Antonarakis S. E. Detection of mutations in the factor VIII gene using single-stranded conformational polymorphism (SSCP). Genomics. 1992 Jul;13(3):909–911. doi: 10.1016/0888-7543(92)90189-y. [DOI] [PubMed] [Google Scholar]
  23. Figueiredo M. S., Bernardi F., Zago M. A. A novel deletion of FVIII gene associated with variable levels of FVIII inhibitor. Eur J Haematol. 1992 Mar;48(3):152–154. doi: 10.1111/j.1600-0609.1992.tb00587.x. [DOI] [PubMed] [Google Scholar]
  24. Fodde R., Losekoot M. Mutation detection by denaturing gradient gel electrophoresis (DGGE). Hum Mutat. 1994;3(2):83–94. doi: 10.1002/humu.1380030202. [DOI] [PubMed] [Google Scholar]
  25. Gitschier J., Kogan S., Levinson B., Tuddenham E. G. Mutations of factor VIII cleavage sites in hemophilia A. Blood. 1988 Sep;72(3):1022–1028. [PubMed] [Google Scholar]
  26. Gitschier J., Levinson B., Lehesjoki A. E., De La Chapelle A. Mosaicism and sporadic haemophilia: implications for carrier determination. Lancet. 1989 Feb 4;1(8632):273–274. doi: 10.1016/s0140-6736(89)91279-8. [DOI] [PubMed] [Google Scholar]
  27. Gitschier J., Wood W. I., Goralka T. M., Wion K. L., Chen E. Y., Eaton D. H., Vehar G. A., Capon D. J., Lawn R. M. Characterization of the human factor VIII gene. Nature. 1984 Nov 22;312(5992):326–330. doi: 10.1038/312326a0. [DOI] [PubMed] [Google Scholar]
  28. Gitschier J., Wood W. I., Shuman M. A., Lawn R. M. Identification of a missense mutation in the factor VIII gene of a mild hemophiliac. Science. 1986 Jun 13;232(4756):1415–1416. doi: 10.1126/science.3012775. [DOI] [PubMed] [Google Scholar]
  29. Gitschier J., Wood W. I., Tuddenham E. G., Shuman M. A., Goralka T. M., Chen E. Y., Lawn R. M. Detection and sequence of mutations in the factor VIII gene of haemophiliacs. 1985 May 30-Jun 5Nature. 315(6018):427–430. doi: 10.1038/315427a0. [DOI] [PubMed] [Google Scholar]
  30. Goodeve A. C., Preston F. E., Peake I. R. Factor VIII gene rearrangements in patients with severe haemophilia A. Lancet. 1994 Feb 5;343(8893):329–330. doi: 10.1016/s0140-6736(94)91165-7. [DOI] [PubMed] [Google Scholar]
  31. Green P. M., Montandon A. J., Bentley D. R., Giannelli F. Genetics and molecular biology of haemophilias A and B. Blood Coagul Fibrinolysis. 1991 Aug;2(4):539–565. doi: 10.1097/00001721-199108000-00007. [DOI] [PubMed] [Google Scholar]
  32. Grover H., Phillips M. A., Lillicrap D. P., Giles A. R., Garvey M. B., Teitel J., Rivard G., Blanchette V., White B. N., Holden J. J. Carrier detection of haemophilia A using DNA markers in families with an isolated affected male. Clin Genet. 1987 Jul;32(1):10–19. doi: 10.1111/j.1399-0004.1987.tb03316.x. [DOI] [PubMed] [Google Scholar]
  33. Handyside A. H., Pattinson J. K., Penketh R. J., Delhanty J. D., Winston R. M., Tuddenham E. G. Biopsy of human preimplantation embryos and sexing by DNA amplification. Lancet. 1989 Feb 18;1(8634):347–349. doi: 10.1016/s0140-6736(89)91723-6. [DOI] [PubMed] [Google Scholar]
  34. Hayashi K., Yandell D. W. How sensitive is PCR-SSCP? Hum Mutat. 1993;2(5):338–346. doi: 10.1002/humu.1380020503. [DOI] [PubMed] [Google Scholar]
  35. Higuchi M., Antonarakis S. E., Kasch L., Oldenburg J., Economou-Petersen E., Olek K., Arai M., Inaba H., Kazazian H. H., Jr Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8307–8311. doi: 10.1073/pnas.88.19.8307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Higuchi M., Kazazian H. H., Jr, Kasch L., Warren T. C., McGinniss M. J., Phillips J. A., 3rd, Kasper C., Janco R., Antonarakis S. E. Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7405–7409. doi: 10.1073/pnas.88.16.7405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Higuchi M., Kazazian H. H., Jr, Kasch L., Warren T. C., McGinniss M. J., Phillips J. A., 3rd, Kasper C., Janco R., Antonarakis S. E. Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7405–7409. doi: 10.1073/pnas.88.16.7405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Higuchi M., Kochhan L., Olek K. A somatic mosaic for haemophilia A detected at the DNA level. Mol Biol Med. 1988 Feb;5(1):23–27. [PubMed] [Google Scholar]
  39. Higuchi M., Kochhan L., Schwaab R., Egli H., Brackmann H. H., Horst J., Olek K. Molecular defects in hemophilia A: identification and characterization of mutations in the factor VIII gene and family analysis. Blood. 1989 Aug 15;74(3):1045–1051. [PubMed] [Google Scholar]
  40. Hoyer L. W. Hemophilia A. N Engl J Med. 1994 Jan 6;330(1):38–47. doi: 10.1056/NEJM199401063300108. [DOI] [PubMed] [Google Scholar]
  41. Inaba H., Fujimaki M., Kazazian H. H., Jr, Antonarakis S. E. Mild hemophilia A resulting from Arg-to-Leu substitution in exon 26 of the factor VIII gene. Hum Genet. 1989 Mar;81(4):335–338. doi: 10.1007/BF00283686. [DOI] [PubMed] [Google Scholar]
  42. Jonsdottir S., Diamond C., Levinson B., Magnusson S., Jensson O., Gitschier J. Missense mutations causing mild hemophilia A in Iceland detected by denaturing gradient gel electrophoresis. Hum Mutat. 1992;1(6):506–508. doi: 10.1002/humu.1380010610. [DOI] [PubMed] [Google Scholar]
  43. Kamisue S., Shima M., Nishimura T., Tanaka I., Nakai H., Morichika S., Takata N., Kuramoto A., Yoshioka A. Abnormal factor VIII Hiroshima: defect in crucial proteolytic cleavage by thrombin at Arg1689 detected by a novel ELISA. Br J Haematol. 1994 Jan;86(1):106–111. doi: 10.1111/j.1365-2141.1994.tb03259.x. [DOI] [PubMed] [Google Scholar]
  44. Kazazian H. H., Jr, Wong C., Youssoufian H., Scott A. F., Phillips D. G., Antonarakis S. E. Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man. Nature. 1988 Mar 10;332(6160):164–166. doi: 10.1038/332164a0. [DOI] [PubMed] [Google Scholar]
  45. Kogan S., Gitschier J. Mutations and a polymorphism in the factor VIII gene discovered by denaturing gradient gel electrophoresis. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2092–2096. doi: 10.1073/pnas.87.6.2092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Krepelová A., Vorlová Z., Acquila M., Mori P. GAA(Glu)272----AAA(Lys) and CGA(Arg)1941----CAA(Gln) in the factor VIII gene in two haemophilia A patients of Czech origin. Br J Haematol. 1992 Jul;81(3):458–458. [PubMed] [Google Scholar]
  47. Krepelová A., Vorlová Z., Zavadil J., Brdicka R. Factor VIII gene deletions in haemophilia A patients in Czechoslovakia. Br J Haematol. 1992 Jun;81(2):271–276. doi: 10.1111/j.1365-2141.1992.tb08219.x. [DOI] [PubMed] [Google Scholar]
  48. Lakich D., Kazazian H. H., Jr, Antonarakis S. E., Gitschier J. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nat Genet. 1993 Nov;5(3):236–241. doi: 10.1038/ng1193-236. [DOI] [PubMed] [Google Scholar]
  49. Lalloz M. R., McVey J. H., Pattinson J. K., Tuddenham E. G. Haemophilia A diagnosis by analysis of a hypervariable dinucleotide repeat within the factor VIII gene. Lancet. 1991 Jul 27;338(8761):207–211. doi: 10.1016/0140-6736(91)90348-s. [DOI] [PubMed] [Google Scholar]
  50. Lavergne J. M., Bahnak B. R., Vidaud M., Laurian Y., Meyer D. A directed search for mutations in hemophilia A using restriction enzyme analysis and denaturing gradient gel electrophoresis. A study of seven exons in the factor VIII gene of 170 cases. Nouv Rev Fr Hematol. 1992;34(1):85–91. [PubMed] [Google Scholar]
  51. Levinson B., Kenwrick S., Gamel P., Fisher K., Gitschier J. Evidence for a third transcript from the human factor VIII gene. Genomics. 1992 Nov;14(3):585–589. doi: 10.1016/s0888-7543(05)80155-7. [DOI] [PubMed] [Google Scholar]
  52. Levinson B., Kenwrick S., Lakich D., Hammonds G., Jr, Gitschier J. A transcribed gene in an intron of the human factor VIII gene. Genomics. 1990 May;7(1):1–11. doi: 10.1016/0888-7543(90)90512-s. [DOI] [PubMed] [Google Scholar]
  53. Lin S. W., Lin S. R., Shen M. C. Characterization of genetic defects of hemophilia A in patients of Chinese origin. Genomics. 1993 Dec;18(3):496–504. [PubMed] [Google Scholar]
  54. Ljung R. C. Intron 22 inversions and haemophilia. Lancet. 1994 Mar 26;343(8900):791–791. [PubMed] [Google Scholar]
  55. Lynch C. M., Israel D. I., Kaufman R. J., Miller A. D. Sequences in the coding region of clotting factor VIII act as dominant inhibitors of RNA accumulation and protein production. Hum Gene Ther. 1993 Jun;4(3):259–272. doi: 10.1089/hum.1993.4.3-259. [DOI] [PubMed] [Google Scholar]
  56. McGinniss M. J., Kazazian H. H., Jr, Hoyer L. W., Bi L., Inaba H., Antonarakis S. E. Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A. Genomics. 1993 Feb;15(2):392–398. doi: 10.1006/geno.1993.1073. [DOI] [PubMed] [Google Scholar]
  57. Mikami S., Nishimura T., Naka H., Kuze K., Fukui H. A deletion involving intron 13 and exon 14 of factor VIII gene in a haemophiliac with anti-factor VIII antibody. Jinrui Idengaku Zasshi. 1988 Dec;33(4):401–407. doi: 10.1007/BF01897780. [DOI] [PubMed] [Google Scholar]
  58. Mikami S., Nishimura T., Naka H., Kuze K., Fukui H., Tone M., Hashimoto-Gotoh T. Nonsense mutation in factor VIII gene of a severe haemophiliac patient with anti-factor VIII antibody. Jinrui Idengaku Zasshi. 1988 Dec;33(4):409–415. doi: 10.1007/BF01897781. [DOI] [PubMed] [Google Scholar]
  59. Millar D. S., Kakkar V. V., Cooper D. N. Screening for inversions in the factor VIII (F8) gene causing severe haemophilia A. Blood Coagul Fibrinolysis. 1994 Apr;5(2):239–242. doi: 10.1097/00001721-199404000-00013. [DOI] [PubMed] [Google Scholar]
  60. Millar D. S., Steinbrecher R. A., Wieland K., Grundy C. B., Martinowitz U., Krawczak M., Zoll B., Whitmore D., Stephenson J., Mibashan R. S. The molecular genetic analysis of haemophilia A; characterization of six partial deletions in the factor VIII gene. Hum Genet. 1990 Dec;86(2):219–227. doi: 10.1007/BF00197709. [DOI] [PubMed] [Google Scholar]
  61. Millar D. S., Zoll B., Martinowitz U., Kakkar V. V., Cooper D. N. The molecular genetics of haemophilia A: screening for point mutations in the factor VIII gene using the restriction enzyme TaqI. Hum Genet. 1991 Sep;87(5):607–612. doi: 10.1007/BF00209022. [DOI] [PubMed] [Google Scholar]
  62. Nafa K., Baudis M., Deburgrave N., Bardin J. M., Sultan Y., Kaplan J. C., Delpech M. A novel mutation (Arg-->Leu in exon 18) in factor VIII gene responsible for moderate hemophilia A. Hum Mutat. 1992;1(1):77–78. doi: 10.1002/humu.1380010114. [DOI] [PubMed] [Google Scholar]
  63. Nafa K., Meriane F., Reghis A., Benabadji M., Demenais F., Guilloud-Bataille M., Sultan Y., Kaplan J. C., Delpech M. Investigation of factor VIII:C gene restriction fragment length polymorphisms and search for deletions in hemophiliac subjects in Algeria. Hum Genet. 1990 Apr;84(5):401–405. doi: 10.1007/BF00195808. [DOI] [PubMed] [Google Scholar]
  64. Naylor J. A., Green P. M., Montandon A. J., Rizza C. R., Giannelli F. Detection of three novel mutations in two haemophilia A patients by rapid screening of whole essential region of factor VIII gene. Lancet. 1991 Mar 16;337(8742):635–639. doi: 10.1016/0140-6736(91)92450-g. [DOI] [PubMed] [Google Scholar]
  65. Naylor J. A., Green P. M., Rizza C. R., Giannelli F. Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients. Hum Mol Genet. 1993 Jan;2(1):11–17. doi: 10.1093/hmg/2.1.11. [DOI] [PubMed] [Google Scholar]
  66. Naylor J. A., Green P. M., Rizza C. R., Giannelli F. Factor VIII gene explains all cases of haemophilia A. Lancet. 1992 Oct 31;340(8827):1066–1067. doi: 10.1016/0140-6736(92)93080-7. [DOI] [PubMed] [Google Scholar]
  67. Naylor J., Brinke A., Hassock S., Green P. M., Giannelli F. Characteristic mRNA abnormality found in half the patients with severe haemophilia A is due to large DNA inversions. Hum Mol Genet. 1993 Nov;2(11):1773–1778. doi: 10.1093/hmg/2.11.1773. [DOI] [PubMed] [Google Scholar]
  68. Oldenburg J., Schwaab R., Grimm T., Zerres K., Hakenberg P., Brackmann H. H., Olek K. Direct and indirect estimation of the sex ratio of mutation frequencies in hemophilia A. Am J Hum Genet. 1993 Dec;53(6):1229–1238. [PMC free article] [PubMed] [Google Scholar]
  69. Pattinson J. K., McVey J. H., Boon M., Ajani A., Tuddenham E. G. CRM+ haemophilia A due to a missense mutation (372----Cys) at the internal heavy chain thrombin cleavage site. Br J Haematol. 1990 May;75(1):73–77. doi: 10.1111/j.1365-2141.1990.tb02618.x. [DOI] [PubMed] [Google Scholar]
  70. Pattinson J. K., Millar D. S., McVey J. H., Grundy C. B., Wieland K., Mibashan R. S., Martinowitz U., Tan-Un K., Vidaud M., Goossens M. The molecular genetic analysis of hemophilia A: a directed search strategy for the detection of point mutations in the human factor VIII gene. Blood. 1990 Dec 1;76(11):2242–2248. [PubMed] [Google Scholar]
  71. Paynton C., Sarkar G., Sommer S. S. Identification of mutations in two families with sporadic hemophilia A. Hum Genet. 1991 Aug;87(4):397–400. doi: 10.1007/BF00197155. [DOI] [PubMed] [Google Scholar]
  72. Peake I. R., Lillicrap D. P., Boulyjenkov V., Briët E., Chan V., Ginter E. K., Kraus E. M., Ljung R., Mannucci P. M., Nicolaides K. Report of a joint WHO/WFH meeting on the control of haemophilia: carrier detection and prenatal diagnosis. Blood Coagul Fibrinolysis. 1993 Apr;4(2):313–344. doi: 10.1097/00001721-199304000-00013. [DOI] [PubMed] [Google Scholar]
  73. Pieneman W. C., Reitsma P. H., Briët E. Double strand conformation polymorphism (DSCP) detects two point mutations at codon 280 (AAC-->ATC) and at codon 431 (TAC-->AAC) of the blood coagulation factor VIII gene. Thromb Haemost. 1993 May 3;69(5):473–475. [PubMed] [Google Scholar]
  74. Reiner A. P., Stray S. M., Thompson A. R. Three missense mutations in Arg codons of the factor VIII genes of mild to moderately severe hemophilia A patients. Thromb Res. 1992 Apr 1;66(1):93–99. doi: 10.1016/0049-3848(92)90159-8. [DOI] [PubMed] [Google Scholar]
  75. Reiner A. P., Thompson A. R. Screening for nonsense mutations in patients with severe hemophilia A can provide rapid, direct carrier detection. Hum Genet. 1992 Apr;89(1):88–94. doi: 10.1007/BF00207049. [DOI] [PubMed] [Google Scholar]
  76. Rosendaal F. R., Bröcker-Vriends A. H., van Houwelingen J. C., Smit C., Varekamp I., van Dijck H., Suurmeijer T. P., Vandenbroucke J. P., Briët E. Sex ratio of the mutation frequencies in haemophilia A: estimation and meta-analysis. Hum Genet. 1990 Dec;86(2):139–146. doi: 10.1007/BF00197695. [DOI] [PubMed] [Google Scholar]
  77. Schwaab R., Ludwig M., Kochhan L., Oldenburg J., McVey J. H., Egli H., Brackmann H. H., Olek K. Detection and characterisation of two missense mutations at a cleavage site in the factor VIII light chain. Thromb Res. 1991 Feb 1;61(3):225–234. doi: 10.1016/0049-3848(91)90098-h. [DOI] [PubMed] [Google Scholar]
  78. Schwaab R., Oldenburg J., Tuddenham E. G., Brackmann H. H., Olek K. Mutations in haemophilia A. Br J Haematol. 1993 Mar;83(3):450–458. doi: 10.1111/j.1365-2141.1993.tb04670.x. [DOI] [PubMed] [Google Scholar]
  79. Shima M., Ware J., Yoshioka A., Fukui H., Fulcher C. A. An arginine to cysteine amino acid substitution at a critical thrombin cleavage site in a dysfunctional factor VIII molecule. Blood. 1989 Oct;74(5):1612–1617. [PubMed] [Google Scholar]
  80. Sommer S. S., Sobell J. L. Application of DNA-based diagnosis to patient care: the example of hemophilia A. Mayo Clin Proc. 1987 May;62(5):387–404. doi: 10.1016/s0025-6196(12)65443-3. [DOI] [PubMed] [Google Scholar]
  81. Tizzano E. F., Altisent C., Tusell J., Domènech M., Baiget M. Intron 22 inversions and haemophilia. Lancet. 1994 Mar 26;343(8900):792–792. [PubMed] [Google Scholar]
  82. Toole J. J., Knopf J. L., Wozney J. M., Sultzman L. A., Buecker J. L., Pittman D. D., Kaufman R. J., Brown E., Shoemaker C., Orr E. C. Molecular cloning of a cDNA encoding human antihaemophilic factor. Nature. 1984 Nov 22;312(5992):342–347. doi: 10.1038/312342a0. [DOI] [PubMed] [Google Scholar]
  83. Toole J. J., Knopf J. L., Wozney J. M., Sultzman L. A., Buecker J. L., Pittman D. D., Kaufman R. J., Brown E., Shoemaker C., Orr E. C. Molecular cloning of a cDNA encoding human antihaemophilic factor. Nature. 1984 Nov 22;312(5992):342–347. doi: 10.1038/312342a0. [DOI] [PubMed] [Google Scholar]
  84. Traystman M. D., Higuchi M., Kasper C. K., Antonarakis S. E., Kazazian H. H., Jr Use of denaturing gradient gel electrophoresis to detect point mutations in the factor VIII gene. Genomics. 1990 Feb;6(2):293–301. doi: 10.1016/0888-7543(90)90569-g. [DOI] [PubMed] [Google Scholar]
  85. Tuddenham E. G., Cooper D. N., Gitschier J., Higuchi M., Hoyer L. W., Yoshioka A., Peake I. R., Schwaab R., Olek K., Kazazian H. H. Haemophilia A: database of nucleotide substitutions, deletions, insertions and rearrangements of the factor VIII gene. Nucleic Acids Res. 1991 Sep 25;19(18):4821–4833. doi: 10.1093/nar/19.18.4821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Wehnert M., Herrmann F. H., Wulff K. Partial deletions of factor VIII gene as molecular diagnostic markers in haemophilia A. Dis Markers. 1989 Apr-Jun;7(2):113–117. [PubMed] [Google Scholar]
  87. Woods-Samuels P., Kazazian H. H., Jr, Antonarakis S. E. Nonhomologous recombination in the human genome: deletions in the human factor VIII gene. Genomics. 1991 May;10(1):94–101. doi: 10.1016/0888-7543(91)90489-2. [DOI] [PubMed] [Google Scholar]
  88. Youssoufian H., Antonarakis S. E., Aronis S., Tsiftis G., Phillips D. G., Kazazian H. H., Jr Characterization of five partial deletions of the factor VIII gene. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3772–3776. doi: 10.1073/pnas.84.11.3772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Youssoufian H., Antonarakis S. E., Bell W., Griffin A. M., Kazazian H. H., Jr Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides. Am J Hum Genet. 1988 May;42(5):718–725. [PMC free article] [PubMed] [Google Scholar]
  90. Youssoufian H., Kasper C. K., Phillips D. G., Kazazian H. H., Jr, Antonarakis S. E. Restriction endonuclease mapping of six novel deletions of the factor VIII gene in hemophilia A. Hum Genet. 1988 Oct;80(2):143–148. doi: 10.1007/BF00702857. [DOI] [PubMed] [Google Scholar]
  91. Youssoufian H., Kazazian H. H., Jr, Patel A., Aronis S., Tsiftis G., Hoyer L. W., Antonarakis S. E. Mild hemophilia A associated with a cryptic donor splice site mutation in intron 4 of the factor VIII gene. Genomics. 1988 Jan;2(1):32–36. doi: 10.1016/0888-7543(88)90106-1. [DOI] [PubMed] [Google Scholar]
  92. Youssoufian H., Kazazian H. H., Jr, Phillips D. G., Aronis S., Tsiftis G., Brown V. A., Antonarakis S. E. Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots. 1986 Nov 27-Dec 3Nature. 324(6095):380–382. doi: 10.1038/324380a0. [DOI] [PubMed] [Google Scholar]
  93. Youssoufian H., Wong C., Aronis S., Platokoukis H., Kazazian H. H., Jr, Antonarakis S. E. Moderately severe hemophilia A resulting from Glu----Gly substitution in exon 7 of the factor VIII gene. Am J Hum Genet. 1988 Jun;42(6):867–871. [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES