title: The spectrum of mutations and molecular pathogenesis of hemophilia A in 181 Portuguese patients.
abstract: 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.
authors.affiliation: Centro de Genética Humana, Instituto Nacional de Saúde, Lisboa, Portugal. dezso.david@insa.min-saude.pt
authors.forename: Dezsö
authors.initials: D
authors.lastname: David
authors.forename: Célia
authors.initials: C
authors.lastname: Ventura
authors.forename: Isabel
authors.initials: I
authors.lastname: Moreira
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Diniz
authors.forename: Margarida
authors.initials: M
authors.lastname: Antunes
authors.forename: Alice
authors.initials: A
authors.lastname: Tavares
authors.forename: Fernando
authors.initials: F
authors.lastname: Araújo
authors.forename: Sara
authors.initials: S
authors.lastname: Morais
authors.forename: Manuel
authors.initials: M
authors.lastname: Campos
authors.forename: João
authors.initials: J
authors.lastname: Lavinha
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Kemball-Cook
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D007446:Chromosome Inversion; D018389:Codon, Nonsense; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005167:Factor VII / Q000032:analysis; D005169:Factor VIII / Q000235:genetics*; D005190:Family; D005260:Female; D006467:Hemophilia A / Q000097:blood* / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011174:Portugal; D015183:Restriction Mapping
chemical_list: D018389:Codon, Nonsense; C078147:F8 protein, human; D005167:Factor VII; D005169:Factor VIII; D004247:DNA