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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 lb‐IX
Author(s) -
Penas Norma,
Pérez Almudena,
GonzálezBoullosa Rosario,
Batlle Javier
Publication year - 2004
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.10455
Subject(s) - von willebrand disease , von willebrand factor , missense mutation , bleeding diathesis , mutation , exon , platelet membrane glycoprotein , point mutation , genetics , platelet , gene , biology , microbiology and biotechnology , glycoprotein , chemistry , immunology
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. Am. J. Hematol. 75:73–77, 2004. © 2004 Wiley‐Liss, Inc.