RESUMO
UNLABELLED: Haemophilia A (HA) is X-chromosome linked bleeding disorders caused by deficiency of the coagulation factor VIII (FVIII). It is caused by FVIII gene intron 22 inversion (Inv22) in approximately 45% and by intron 1 inversion (Inv1) in 5% of the patients. Both inversions occur as a result of intrachromosomal recombination between homologous regions, in intron 1 or 22 and their extragenic copy located telomeric to the FVIII gene. The aim of this study was to analyze the presence of these mutations in 25 HA Costa Rican families. PATIENTS, METHODS: We studied 34 HA patients and 110 unrelated obligate members and possible carriers for the presence of Inv22or Inv1. Standard analyses of the factor VIII gene were used incl. Southern blot and long-range polymerase chain reaction for inversion analysis. RESULTS: We found altered Inv22 restriction profiles in 21 patients and 37 carriers. It was found type 1 and type 2 of the inversion of Inv22. During the screening for Inv1 among the HA patient, who were Inv22 negative, we did not found this mutation. DISCUSSION: Our data highlight the importance of the analysis of Inv22 for their association with development of inhibitors in the HA patients and we are continuous searching of Inv1 mutation. This knowledge represents a step for genetic counseling and prevention of the inhibitor development.
Assuntos
Fator VIII/genética , Hemofilia A/genética , Cromossomos Humanos X/genética , Costa Rica , DNA/sangue , DNA/genética , DNA/isolamento & purificação , Feminino , Hemofilia A/sangue , Humanos , Íntrons/genética , Masculino , Linhagem , Reação em Cadeia da Polimerase/métodos , Mapeamento por Restrição , Índice de Gravidade de DoençaRESUMO
Haemophilia is the most frequent hereditary haemorrhagic illness and it is due to the deficiency of coagulation factors VIII (haemophilia A, HA) or IX (haemophilia B, HB). The prevalence of this disease varies according to the country, those having better survival rates having also higher prevalences. Specifically in Costa Rica, there are around 130 HA and 30 HB families. This study reports the prevalence and a spatial distribution analysis of both types of the disease in this country. The prevalence of haemophilia in this country is 7 cases per 100000 men, for HA it is 6 cases per 100000 and for HB it is 1 case per 100000 male inhabitants. The prevalence of this disease is low when compared with other populations. This low prevalence could be due to the many patients that have died because of infection with human immunodeficiency virus during the 1980s. The prevalence of haemophilia in Costa Rica is almost one half of that present in developed countries. Nevertheless, the ratio between HA and HB follows world tendency: 5:1. In this study, nationwide geographical distribution maps were drawn in order to visualize the origin of severe cases and how this influences the pattern of distribution for both types of haemophilia. By means of these maps, it was possible to state that there is no association between the sites of maximum prevalence of mutated alleles and ethnicity. With this study, haemophilia prevalence distribution maps can be used to improve efforts for the establishment of hemophilia clinics or specialized health centers in those areas which hold the highest prevalences in this country. Also, this knowledge can be applied to improve treatment skills and offer the possibility of developing focused genetic counseling for these populations.
Assuntos
Hemofilia A/epidemiologia , Adolescente , Adulto , Criança , Costa Rica/epidemiologia , Demografia , Fator VIII/genética , Geografia , Hemofilia A/complicações , Hemofilia A/mortalidade , Hemofilia B/epidemiologia , Hemofilia B/genética , Hemofilia B/mortalidade , Hepatite C/complicações , Hepatite C/epidemiologia , Humanos , Masculino , Prevalência , Índice de Gravidade de DoençaRESUMO
Chromosome analyses were performed on bone marrow and peripheral blood leucocytes of 117 patients with acute and chronic leukemias and myelodysplastic, myeloproliferative and hypereosinophilic syndromes, diagnosed in a Costa Rican hospital from May 1990 to July 1992. Cytogenetic diagnosis was achieved in 69.5% of the 131 samples, the karyotype was normal in half of them. The most common chromosomal defect was the Philadelphia translocation, found in 80.5% of the patients with chronic myelocitic leukemia as referral diagnosis and in some other cases. Other primary and secondary chromosomal abnormalities were less frequent. The karyotype analysis proved useful in clinical evaluation and management.
