Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Sep 1;90(17):7937–7940. doi: 10.1073/pnas.90.17.7937

Mutations of von Willebrand factor gene in families with von Willebrand disease in the Aland Islands.

Z P Zhang 1, M Blombäck 1, D Nyman 1, M Anvret 1
PMCID: PMC47262  PMID: 8367445

Abstract

Patients with von Willebrand disease in four families in the Aland Islands, including the original family that was described in 1926 by the Finnish physician von Willebrand, were screened for mutations in the Swedish "hot-spot" regions (exons 18, 28, 32, 43, and 45) of the von Willebrand factor gene. One cytosine deletion in exon 18 was detected in each of these families. Linkage analysis and genealogical studies suggest that the deletion present in these four families probably has an origin in common with the mutations in the Swedish patients. Apart from the deletion in exon 18, two close transitions (G-->A at S1263 and C-->T at P1266) in exon 28 on the same chromosome were identified in one individual who married into the original family and in his two children. The transitions could be due to a recombination between the von Willebrand factor gene and its pseudogene.

Full text

PDF

Images in this article

7939Fig. 1
on p.7939
7939Fig. 2
on p.7939
7939Fig. 3
on p.7939

Selected References

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

  1. Anvret M., Blombäck M., Lindstedt M., Söderlind E., Tapper-Persson M., Thelander A. C. Genetic and blood coagulation characterization of "Swedish" families with von Willebrand's disease types I and III: new aspects of heredity. Hum Genet. 1992 May;89(2):147–154. doi: 10.1007/BF00217114. [DOI] [PubMed] [Google Scholar]
  2. BLOMBACK M. Studies on antihemophilic globulin. Acta Paediatr Suppl. 1958 Apr;47(Suppl 114):1–32. [PubMed] [Google Scholar]
  3. Blombäck M., Eneroth P., Andersson O., Anvret M. On laboratory problems in diagnosing mild von Willebrand's disease. Am J Hematol. 1992 Jun;40(2):117–120. doi: 10.1002/ajh.2830400208. [DOI] [PubMed] [Google Scholar]
  4. CORNU P., LARRIEU M. J., CAEN J., BERNARD J. [Willebrand's disease. Clinical, genetic and biological study (apropos of 22 cases)]. Nouv Rev Fr Hematol. 1961 Mar-Apr;1:231–262. [PubMed] [Google Scholar]
  5. JURGENS R., FORSIUS H. Untersuchungen über die konstitutionelle Thrombopathie (v. Willebrand-Jürgens) auf den Alandsinseln. Schweiz Med Wochenschr. 1951 Dec 15;81(50):1248–1253. [PubMed] [Google Scholar]
  6. JURGENS R., LEHMANN W., WEGELIUS O., ERIKSSON A. W., HIEPLER E. Mitteilung über den Mangel an antihämophilem Globulin (Factor VIII) bei der Aaländischen Thrombopathie (v. Willebrand-Jürgens). Thromb Diath Haemorrh. 1957 Aug 15;1(2):257–260. [PubMed] [Google Scholar]
  7. Mancuso D. J., Tuley E. A., Westfield L. A., Lester-Mancuso T. L., Le Beau M. M., Sorace J. M., Sadler J. E. Human von Willebrand factor gene and pseudogene: structural analysis and differentiation by polymerase chain reaction. Biochemistry. 1991 Jan 8;30(1):253–269. doi: 10.1021/bi00215a036. [DOI] [PubMed] [Google Scholar]
  8. Mancuso D. J., Tuley E. A., Westfield L. A., Worrall N. K., Shelton-Inloes B. B., Sorace J. M., Alevy Y. G., Sadler J. E. Structure of the gene for human von Willebrand factor. J Biol Chem. 1989 Nov 25;264(33):19514–19527. [PubMed] [Google Scholar]
  9. NILSSON I. M., BLOMBACK M., BLOMBACK B. v. Willebrand's disease in Sweden; its pathogenesis and treatment. Acta Med Scand. 1959 Jun 30;164:263–278. [PubMed] [Google Scholar]
  10. NILSSON I. M., BLOMBACK M., JORPES E., BLOMBACK B., JOHANSSON S. A. Von Willebrand's disease and its correction with human plasma fraction 1-0. Acta Med Scand. 1957 Nov 29;159(3):179–188. doi: 10.1111/j.0954-6820.1957.tb00123.x. [DOI] [PubMed] [Google Scholar]
  11. NILSSON I. M., BLOMBACK M., VON FRANCKEN I. On an inherited autosomal hemorrhagic diathesis with antihemophilic globulin (AHG) deficiency and prolonged bleeding time. Acta Med Scand. 1957 Oct 30;159(1):35–57. doi: 10.1111/j.0954-6820.1957.tb00532.x. [DOI] [PubMed] [Google Scholar]
  12. Nyman D., Eriksson A. W., Blombäck M., Frants R. R., Wahlberg P. Recent investigations of the first bleeder family in Aland (Finland) described by von Willebrand. Thromb Haemost. 1981 Feb 23;45(1):73–76. [PubMed] [Google Scholar]
  13. Nyman D., Eriksson A. W., Lehmann W., Blombäck M. Inherited defective platelet aggregation with arachidonate as the main expression of a defective metabolism of arachidonic acid. Thromb Res. 1979;14(4-5):739–746. doi: 10.1016/0049-3848(79)90129-4. [DOI] [PubMed] [Google Scholar]
  14. SINGER K., RAMOT B. Pseudohemophilia type B; hereditary hemorrhagic diathesis characterized by prolonged bleeding time and decrease in antihemophilic factor. AMA Arch Intern Med. 1956 Jun;97(6):715–725. doi: 10.1001/archinte.1956.00250240067006. [DOI] [PubMed] [Google Scholar]
  15. Wahlberg T. B., Savidge G. F., Blombäck M., Wiechel B. Influence of age, sex and blood groups on 15 blood coagulation laboratory variables in a reference material composed of 80 blood donors. Vox Sang. 1980 Dec;39(6):301–308. doi: 10.1111/j.1423-0410.1980.tb02966.x. [DOI] [PubMed] [Google Scholar]
  16. Zhang Z. P., Deng L. P., Blombäck M., Anvret M. Dinucleotide repeat polymorphism in the promoter region of the human von Willebrand factor gene (vWF gene). Hum Mol Genet. 1992 Dec;1(9):780–780. doi: 10.1093/hmg/1.9.780. [DOI] [PubMed] [Google Scholar]
  17. Zhang Z. P., Falk G., Blombäck M., Egberg N., Anvret M. A single cytosine deletion in exon 18 of the von Willebrand factor gene is the most common mutation in Swedish vWD type III patients. Hum Mol Genet. 1992 Dec;1(9):767–768. doi: 10.1093/hmg/1.9.767. [DOI] [PubMed] [Google Scholar]
  18. Zhang Z. P., Lindstedt M., Falk G., Blombäck M., Egberg N., Anvret M. Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I. Am J Hum Genet. 1992 Oct;51(4):850–858. [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES