An Alu-mediated novel large deletion is the most frequent cause of type 3 von Willebrand disease in Hungary

Adrienn Mohl, R. Marschalek, T. Masszi, E. Nagy, T. Obser, F. Oyen, K. Sallai, I. Bodó, R. Schneppenheim

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: We studied 24 Hungarian patients from 23 unrelated families to identify the genetic background of the entire type 3 von Willebrand disease (VWD) population in this country. The current report focuses on the molecular characterization of a novel large deletion. Results: A large partial deletion (delExon1-3) of the 5′-region of the von Willebrand factor gene (VWF) was detected in 12/48 alleles (25% of all type 3 alleles). The 5′-deletion breakpoint is located in the untranslated region between VWF and CD9, whereas the 3′ breakpoint is in intron 3 of VWF. Analysis of the breakpoints showed Alu Y and Alu SP repetitive sequences at the ends of the deletion, suggesting that a recombination event caused the subsequent loss of the 35-kb fragment. DelExon1-3 was not found in any of the other screened populations. Conclusion: We report a large novel deletion including exons 1, 2 and 3 of VWF commonly causing type.3 VWD in the Hungarian population. This mutation, probably caused by an Alu-mediated recombination event, and subsequently distributed in Hungary by a founder effect, seems to be unique to Hungarian patients with a high allele frequency. Together, delExon1-3 and 2435delC make up 37.5% of the genetic defects in Hungarian patients with VWD type.3. This offers a rational approach to molecular testing of relevant families in Hungary.

Original languageEnglish
Pages (from-to)1729-1735
Number of pages7
JournalJournal of Thrombosis and Haemostasis
Volume6
Issue number10
DOIs
Publication statusPublished - 2008

Fingerprint

Type 3 Von Willebrand's Disease
Hungary
von Willebrand Factor
von Willebrand Diseases
Genetic Recombination
Genes
Alleles
Alu Elements
Population
Founder Effect
Untranslated Regions
Gene Frequency
Introns
Exons
Mutation

Keywords

  • Alu sequence
  • Gene deletion
  • Type 3
  • Von Willebrand disease

ASJC Scopus subject areas

  • Hematology

Cite this

An Alu-mediated novel large deletion is the most frequent cause of type 3 von Willebrand disease in Hungary. / Mohl, Adrienn; Marschalek, R.; Masszi, T.; Nagy, E.; Obser, T.; Oyen, F.; Sallai, K.; Bodó, I.; Schneppenheim, R.

In: Journal of Thrombosis and Haemostasis, Vol. 6, No. 10, 2008, p. 1729-1735.

Research output: Contribution to journalArticle

Mohl, Adrienn ; Marschalek, R. ; Masszi, T. ; Nagy, E. ; Obser, T. ; Oyen, F. ; Sallai, K. ; Bodó, I. ; Schneppenheim, R. / An Alu-mediated novel large deletion is the most frequent cause of type 3 von Willebrand disease in Hungary. In: Journal of Thrombosis and Haemostasis. 2008 ; Vol. 6, No. 10. pp. 1729-1735.
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abstract = "Background: We studied 24 Hungarian patients from 23 unrelated families to identify the genetic background of the entire type 3 von Willebrand disease (VWD) population in this country. The current report focuses on the molecular characterization of a novel large deletion. Results: A large partial deletion (delExon1-3) of the 5′-region of the von Willebrand factor gene (VWF) was detected in 12/48 alleles (25{\%} of all type 3 alleles). The 5′-deletion breakpoint is located in the untranslated region between VWF and CD9, whereas the 3′ breakpoint is in intron 3 of VWF. Analysis of the breakpoints showed Alu Y and Alu SP repetitive sequences at the ends of the deletion, suggesting that a recombination event caused the subsequent loss of the 35-kb fragment. DelExon1-3 was not found in any of the other screened populations. Conclusion: We report a large novel deletion including exons 1, 2 and 3 of VWF commonly causing type.3 VWD in the Hungarian population. This mutation, probably caused by an Alu-mediated recombination event, and subsequently distributed in Hungary by a founder effect, seems to be unique to Hungarian patients with a high allele frequency. Together, delExon1-3 and 2435delC make up 37.5{\%} of the genetic defects in Hungarian patients with VWD type.3. This offers a rational approach to molecular testing of relevant families in Hungary.",
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AB - Background: We studied 24 Hungarian patients from 23 unrelated families to identify the genetic background of the entire type 3 von Willebrand disease (VWD) population in this country. The current report focuses on the molecular characterization of a novel large deletion. Results: A large partial deletion (delExon1-3) of the 5′-region of the von Willebrand factor gene (VWF) was detected in 12/48 alleles (25% of all type 3 alleles). The 5′-deletion breakpoint is located in the untranslated region between VWF and CD9, whereas the 3′ breakpoint is in intron 3 of VWF. Analysis of the breakpoints showed Alu Y and Alu SP repetitive sequences at the ends of the deletion, suggesting that a recombination event caused the subsequent loss of the 35-kb fragment. DelExon1-3 was not found in any of the other screened populations. Conclusion: We report a large novel deletion including exons 1, 2 and 3 of VWF commonly causing type.3 VWD in the Hungarian population. This mutation, probably caused by an Alu-mediated recombination event, and subsequently distributed in Hungary by a founder effect, seems to be unique to Hungarian patients with a high allele frequency. Together, delExon1-3 and 2435delC make up 37.5% of the genetic defects in Hungarian patients with VWD type.3. This offers a rational approach to molecular testing of relevant families in Hungary.

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