Genetic Study of von Willebrand Factor in Twenty-two Members of an Argentinian Family

CARBALLO, GONZALO AUGUSTO; WOODS, ADRIANA; VERA, EZEQUIEL; CASAIS, PATRICIA; ALETTI, P; FARÍAS, CRISTINA; KEMPFER, ANA CATALINA; LAZZARI, MARÍA ANGELA

Sydney, Australia

Congreso; XXth International Society on Thrombosis and Haemostasis Congress; 2005

Introduction:  According to the recessive inheritance of the type 2 N von Willebrand disease (VWD 2N), the heterocygotes individuals are frequently asymptomatic, whereas the homocygotes and compound heterocygotes ones show a phenotype appearing hemophilia A (HA). R854Q (G2561A) mutation is the most frequent, with minor bleeding. From a patient presenting two major hemorrhage episodes in surgeries and muco-cutaneous bleeding and family history of mild hemophilia A who came first to control during the 4th month of pregnancy, we re-evaluated the diagnosis of HA in her family, studying the exon 20 in twenty-two members (three generations) of her family. Methods:  Exons 18 to 24 of VWF gen were screened by CSGE technique. Exons showing double band electrophoretic pattern were sequenced (ABI Prism 310 Genetic Analyzer). Results:  Patient DNA showed a heterocygote mutation R854Q in exon 20. In her family, four heterocygote individuals for R854Q were also found: her mother (symptomatic), two asymptomatic brothers and her son (symptomatic, low VWF:FVIIIB). R854Q mutation was absent in her daughter (symptomatic, low VWF:FVIIIB), a son and a brother (asymptomatic and normal VWF:FVIIIB), three cousins (symptomatic males, FVIII within 12–23 U/dL, low VWF:FVIIIB), one asymptomatic cousin, four nephews (one symptomatic and FVIII 5 U/dL), four asymptomatic nieces and two asymptomatic mother's sisters. Conclusion:  We found the heterocygote R854Q mutation in 5 out 22 family members, with a 22.7% of penetrance. A 60% of these patients have clinical symptoms. We should guide the molecular study towards the search of other mutations in the relatives.