TY - JOUR
T1 - Von Willebrand disease type 2M 'Vicenza' in Italian and German patients
T2 - Identification of the first candidate mutation (G3864A; R1205H) in 8 families
AU - Schneppenheim, Reinhard
AU - Federici, Augusto B.
AU - Budde, Ulrich
AU - Castaman, Giancarlo
AU - Drewke, Elke
AU - Krey, Sonja
AU - Mannucci, Pier M.
AU - Riesen, Gabi
AU - Rodeghiero, Francesco
AU - Zieger, Barbara
AU - Zimmermann, Rainer
PY - 2000
Y1 - 2000
N2 - Von Willebrand disease type 2M 'Vicenza' (VWD 2M V) is characterised by autosomal dominant inheritance, low von Willebrand factor (VWF) and the presence of 'supranormal' multimers in plasma. This specific phenotype has been described in Italian and recently also in German patients. The molecular defect is linked to the VWF gene. However, no specific mutations have been identified until now. We analysed the complete coding region and adjacent intron sequences of the VWF gene in Italian families in comparison to German families with VWD 2M V by a PCR-based mutation screening, combined with SSC- and heteroduplex-analysis of exons 2 through 52, followed by direct sequencing. We identified the first heterozygous candidate mutation (G3864A: R1205H) in all affected members of the 7 Italian families and in 1 German patient but not in the unaffected family members nor on 100 chromosomes of normal subjects, suggesting a causal relationship between the mutation and the phenotype. Haplotype identity, with minor deviations in one Italian family, suggests a common but not very recent genetic origin of R1205H.
AB - Von Willebrand disease type 2M 'Vicenza' (VWD 2M V) is characterised by autosomal dominant inheritance, low von Willebrand factor (VWF) and the presence of 'supranormal' multimers in plasma. This specific phenotype has been described in Italian and recently also in German patients. The molecular defect is linked to the VWF gene. However, no specific mutations have been identified until now. We analysed the complete coding region and adjacent intron sequences of the VWF gene in Italian families in comparison to German families with VWD 2M V by a PCR-based mutation screening, combined with SSC- and heteroduplex-analysis of exons 2 through 52, followed by direct sequencing. We identified the first heterozygous candidate mutation (G3864A: R1205H) in all affected members of the 7 Italian families and in 1 German patient but not in the unaffected family members nor on 100 chromosomes of normal subjects, suggesting a causal relationship between the mutation and the phenotype. Haplotype identity, with minor deviations in one Italian family, suggests a common but not very recent genetic origin of R1205H.
KW - Von Willebrand disease type 2M Vicenza
KW - Von Willebrand factor genetics
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M3 - Article
C2 - 10669167
AN - SCOPUS:0033971892
VL - 83
SP - 136
EP - 140
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
SN - 0340-6245
IS - 1
ER -