An Alu-mediated novel large deletion is the most frequent cause of type 3 von Willebrand disease in Hungary.
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.
Mohl
A
A
Semmelweis Medical University, Central Laboratory of Immunology and Haematology, Budapest, Hungary. adrienn.mohl@yahoo.com
Marschalek
R
R
Masszi
T
T
Nagy
E
E
Obser
T
T
Oyen
F
F
Sallai
K
K
Bodó
I
I
Schneppenheim
R
R
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*
D014841:von Willebrand Factor