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.
David
Dezsö
D
Centro de Genética Humana, Instituto Nacional de Saúde, Lisboa, Portugal. dezso.david@insa.min-saude.pt
Ventura
Célia
C
Moreira
Isabel
I
Diniz
Maria J
MJ
Antunes
Margarida
M
Tavares
Alice
A
Araújo
Fernando
F
Morais
Sara
S
Campos
Manuel
M
Lavinha
João
J
Kemball-Cook
Geoffrey
G
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
D018389:Codon, Nonsense; C078147:F8 protein, human; D005167:Factor VII; D005169:Factor VIII; D004247:DNA