Detecção de portadoras e caracterização molecular na hemofilia A em uma população brasileira

AUTOR(ES)
DATA DE PUBLICAÇÃO

1995

RESUMO

The molecular characterization of the mutations in hemophilia A patients is hampered the large size of the factor VIII gene and the great heterogeneity of mutations. First of all we carried out a study of RLFPs for the enzymes BelI and HindIII in 24 families of hemophilia A patients and was possible to detect carriers in 70% of the families. Further in a attempt to elucidate the genetic basis of a distinct population and to perform a precise carrier detection we carried out a study of Brazilian patients with hemophilia A. In this study, we have carried out a protoeol involving multiplex PCR in which 19 exons were amplified in four different combinations followed by non-radioactive SSCP in order to screen for mutations. Southern blotting was used to detect inversion of the factor VITI gene resulting from recombination between copies of the F8A gene located in intron 22 of the factor VITI gene and two copies close telomeric region of chromosome. Forty-two hemophilia A patients (21 with severe and 21 with mild-to-moderate disease) were studied. The inversion of factor VITI occurred in 13 out of 21 patients affected by severe hemophilia A. One patient showed a large extra band in addition to the three bands observed following Southern blotting with the F8A probe. An abnormal electrophoretic pattem of SSCP was detected in 85% and 50% of the patients affected by mild-to-moderate and severe disease, respectivelly. Sixteen different mutations were identified. Eleven mutations were novel and comprised nine point mutations and two small deletions. This study demonstrates that the methodology employed is safe and rapid and has a potential in detecting almost all the genetic defects of the studied hemophiliacs patients

ASSUNTO(S)

hemofilia - brasil - teses

ACESSO AO ARTIGO

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