title: Molecular characterization of Iranian patients with type 3 von Willebrand disease.
abstract: von Willebrand's disease (VWD) type 3 is a rare but severe autosomal-recessive inherited bleeding disorder with a prevalence higher in certain locations where consanguineous marriages are relatively frequent. The genetic defects causing recessive type 3 VWD in 10 unrelated families from Iran have been investigated and the genetic heterogeneity among these patients was evaluated. All exons and their flanking regions of von Willebrand factor gene were amplified by PCR and sequenced using specific primers. Eight patients were fully characterized at the molecular level. Six different gene alterations were identified. All the mutations caused null alleles, three being nonsense mutations (Q104X, Q793X and E1981X), two possible splice site mutations (2443-1G>C and 1110-1G>A) and one small deletion (3237delA). Three of them have not been described previously. Most patients were born from consanguineous marriages and all were homozygous for their mutations. The results confirm that molecular defects in type 3 VWD are heterogeneous with mutations arising randomly within the entire gene.
authors.affiliation: INSERM U770, Faculté de Médecine Paris-Sud, Université Paris-Sud, IFR93, Le Kremlin-Bicêtre, France.
authors.forename: S
authors.initials: S
authors.lastname: Shahbazi
authors.forename: R
authors.initials: R
authors.lastname: Mahdian
authors.forename: F A
authors.initials: FA
authors.lastname: Ala
authors.forename: J-M
authors.initials: JM
authors.lastname: Lavergne
authors.forename: C V
authors.initials: CV
authors.lastname: Denis
authors.forename: O D
authors.initials: OD
authors.lastname: Christophe
mesh_terms: D000328:Adult; D018389:Codon, Nonsense / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D018740:Genetic Heterogeneity; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D015995:Prevalence; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D055815:Young Adult; D056729:von Willebrand Disease, Type 3 / Q000453:epidemiology / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense