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An Alu‐mediated novel large deletion is the most frequent cause of type 3 von Willebrand disease in Hungary
Author(s) -
MOHL A.,
MARSCHALEK R.,
MASSZI T.,
NAGY E.,
OBSER T.,
OYEN F.,
SALLAI K.,
BODÓ I.,
SCHNEPPENHEIM R.
Publication year - 2008
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2008.03107.x
Subject(s) - genetics , breakpoint , von willebrand disease , alu element , exon , biology , allele , population , von willebrand factor , intron , gene , untranslated region , founder effect , mutation , human genome , medicine , genome , immunology , haplotype , rna , chromosomal translocation , platelet , environmental health
Summary. 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.