title: C1272S: a new candidate mutation in type 2A von Willebrand disease that disrupts the disulfide loop responsible for the interaction of VWF with platelet GP Ib-IX.
abstract: Most of type 2A von Willebrand disease (VWD) mutations are clustered within the A2 domain of VWF, encoded by the 3' region of exon 28 of the von Willebrand factor (VWF) gene. A patient with lifelong and severe bleeding diathesis and laboratory data of type 2A VWD is described. The analysis of the complete exon 28 of the VWF gene showed a 3815 G-->C change within the A1 domain, resulting in the C1272S missense mutation in a heterozygous state. The substitution was not found in 100 normal alleles also examined and has not been described previously. This candidate mutation would interrupt the formation of the disulfide loop 1272-1458, which is important in maintaining the adequate conformation of the VWF functional domain that interacts with platelet glycoprotein Ib-IX. Gene expression of this candidate mutation is necessary to confirm its role.
authors.affiliation: Servicio de Hematología del Complejo Hospitalario Universitario Juan Canalejo, A Coruña, Spain.
authors.forename: Norma
authors.initials: N
authors.lastname: Penas
authors.forename: Almudena
authors.initials: A
authors.lastname: Pérez
authors.forename: Rosario
authors.initials: R
authors.lastname: González-Boullosa
authors.forename: Javier
authors.initials: J
authors.lastname: Batlle
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001483:Base Sequence; D004247:DNA / Q000097:blood / Q000235:genetics; D017931:DNA Primers; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D020125:Mutation, Missense; D010641:Phenotype; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D012016:Reference Values; D014842:von Willebrand Diseases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D019038:Platelet Glycoprotein GPIb-IX Complex; D004247:DNA