The Spectrum of Mutations and Molecular Pathogenesis of Hemophilia A in 181 Portuguese Patients

Disease-causing alterations within the F8 gene were identified in 177 hemophilia A families of Portuguese origin. The spectrum of non-inversion F8 mutations in 101 families included 67 different alterations, namely: 36 missense, 8 nonsense and 4 splice site mutations, as well as 19 insertions/deletions. Thirty-four of these mutations are novel. Molecular modeling allowed prediction of the conformational changes introduced by selected amino acid substitutions and their correlation with the patients' phenotypes. The relatively frequent, population-specific, missense mutations together with de novo alterations can lead to significant differences in the spectrum of F8 mutations among different populations.

Keywords

Hemofilia A Portugal Mutação Factor VIII Mapeamento por Restrição Sequência de Bases Inversão Cromossômica Códon Sem Sentido Polimorfismo de Conformação de Filamento Único Polimorfismo Genético Mutação de Sentido Incorrecto Factor VII Processamento Alternativo Família