title: An Alu-mediated novel large deletion is the most frequent cause of type 3 von Willebrand disease in Hungary.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Semmelweis Medical University, Central Laboratory of Immunology and Haematology, Budapest, Hungary. adrienn.mohl@yahoo.com
authors.forename: A
authors.initials: A
authors.lastname: Mohl
authors.forename: R
authors.initials: R
authors.lastname: Marschalek
authors.forename: T
authors.initials: T
authors.lastname: Masszi
authors.forename: E
authors.initials: E
authors.lastname: Nagy
authors.forename: T
authors.initials: T
authors.lastname: Obser
authors.forename: F
authors.initials: F
authors.lastname: Oyen
authors.forename: K
authors.initials: K
authors.lastname: Sallai
authors.forename: I
authors.initials: I
authors.lastname: Bodó
authors.forename: R
authors.initials: R
authors.lastname: Schneppenheim
mesh_terms: D024506:5' Flanking Region; D020087:Alu Elements; D005091:Exons; D005190:Family; D018703:Founder Effect; D017353:Gene Deletion; D005787:Gene Frequency; D006801:Humans; D006814:Hungary; D007438:Introns; D014842:von Willebrand Diseases / Q000145:classification / Q000453:epidemiology / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D014841:von Willebrand Factor