title: Gene defects in 150 unrelated French cases with type 2 von Willebrand disease: from the patient to the gene. INSERM Network on Molecular Abnormalities in von Willebrand Disease.
abstract: Type 2 vWD is defined by qualitative defects of vWF and is subdivided into four subtypes: 2N, 2B, 2A and 2M. The characterization of 150 unrelated French cases with type 2 vWD emphasizes the heterogeneity of this group. In 51 cases of type 2N vWD, new mutations were found not only in the D' domain (Cys25Tyr and Cys95Phe) but also in the D3 domain (Asp116Asn and Cys297Arg). In 42 cases of type 2B vWD, no new mutation was detected. In 45 cases with type 2A phenotype, three new candidate mutations were found in the A2 domain: Gln793Arg, Val841Phe and Leu876Pro. In addition, four new candidate mutations were detected in the A1 domain: Cys509Gly, Arg545His, Arg552Cys and Cys695Tyr. Finally, five new candidate mutations were identified in 12 patients with 2M (or unclassified) phenotype: Leu513Pro, Gly561A1a, Glu596Lys, Arg611Leu and IIe662Phe. For all candidate mutations, expression studies are in progress. This study of a large number of French variants of vWD brings further insight into the relationship between phenotype and genotype.
authors.affiliation: INSERM U. 143, Hôpital Bicêtre, Le Kremlin-Bicêtre, France. dmeyer@infobiogen.fr
authors.forename: D
authors.initials: D
authors.lastname: Meyer
authors.forename: E
authors.initials: E
authors.lastname: Fressinaud
authors.forename: C
authors.initials: C
authors.lastname: Gaucher
authors.forename: J M
authors.initials: JM
authors.lastname: Lavergne
authors.forename: L
authors.initials: L
authors.lastname: Hilbert
authors.forename: A S
authors.initials: AS
authors.lastname: Ribba
authors.forename: S
authors.initials: S
authors.lastname: Jorieux
authors.forename: C
authors.initials: C
authors.lastname: Mazurier
mesh_terms: D000595:Amino Acid Sequence; D005602:France; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D014842:von Willebrand Diseases / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D014841:von Willebrand Factor