RESUMO
BACKGROUND: Genomic inversions are usually balanced, but unusual patterns have been described in haemophilia A (HA) patients for intron 22 (Inv22) and intron 1 (Inv1) inversions leading to the hypothesis of more complex rearrangements involving deletions or duplications. AIM: To characterize five abnormal patterns either in Southern blot and long-range PCR for Inv22 or in PCR for Inv1. MATERIALS AND METHODS: All patients were studied using cytogenetic microarray analysis (CMA). RESULTS: In all cases, CMA analysis found that each inversion was associated with complex Xq28 rearrangement. In three patients, CMA analysis showed large duplication ranging from 230 to 1302 kb and encompassing a various number of contiguous genes among which RAB39B. RAB39B duplication is a strong candidate gene for X-linked intellectual disability (XLID). Surprisingly, none of the severe HA patients with RAB39B duplication reported in this study or in the literature exhibited XLID. We hypothesise that F8 complex rearrangement down regulated RAB39B expression. In the two remaining patients, CMA analysis found Xq28 large deletion (from 285 to 522 kb). Moyamoya syndrome was strongly suspected in one of them who carried BRCC3 deletion. CONCLUSION: Because several F8 neighbouring genes are associated with other pathologies such as XLID and cardiovascular disease, all HA patients where complex Xq28 rearrangement was suspected should be referred to a geneticist for possible utility of a pangenomic study. Such investigation should be carefully considered in genetic counselling in female carriers to assess the risk of transmitting severe HA with a "contiguous gene syndrome".
Assuntos
Análise Citogenética , Fator VIII/genética , Rearranjo Gênico , Aconselhamento Genético , Hemofilia A/genética , Feminino , Hemofilia A/diagnóstico , Humanos , Íntrons/genética , Masculino , Análise de Sequência com Séries de OligonucleotídeosRESUMO
The bleeding phenotype has been suggested to differ between haemophilia A and B. More knowledge on the bleeding phenotype at initiation of treatment is important to optimize patient care. The aim of this study was to investigate the severity of the bleeding phenotype and the variation in bleeding in children with severe or moderate haemophilia A and B. Consecutive, previously untreated patients with severe or moderate haemophilia A and B (factor VIII or IX activity <0.01 or 0.01-0.05 IU mL(-1) respectively) born between January 1st 2000 and January 1st 2010 were included. Primary outcome was severity of bleeding tendency. Secondary outcome was variation in bleeding pattern. A total of 582 patients with severe haemophilia A and 76 with severe haemophilia B did not differ in age at first exposure to clotting factor (0.81 vs. 0.88 years, P = 0.20), age at first bleed (0.82 vs. 0.88 years, P = 0.36), and age at first joint bleed (1.18 vs. 1.20 years, P = 0.59). Patients with moderate haemophilia were older compared to patients with severe haemophilia. In patients with moderate haemophilia there were no clear differences between haemophilia A and B. Severity and variation in bleeding phenotype are similar during the early stage of treatment in patients with severe and moderate haemophilia A and B respectively. The findings imply that children with haemophilia B should be observed and treated as vigilantly as those with haemophilia A.
Assuntos
Hemofilia A/diagnóstico , Hemofilia B/diagnóstico , Hemorragia/patologia , Fenótipo , Criança , Pré-Escolar , Estudos de Coortes , Fator IX/genética , Fator VIII/genética , Feminino , Genótipo , Hemofilia A/tratamento farmacológico , Hemofilia A/genética , Hemofilia B/tratamento farmacológico , Hemofilia B/genética , Hemorragia/diagnóstico , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Sistema de Registros , Índice de Gravidade de DoençaRESUMO
Early predictive factors of HIV infection in infants born to HIV infected mothers were carried out to evaluate the roles of immunological parameters for the diagnosis and prognosis of HIV infection. T-lymphocyte subsets and serum immunoglobulins were studied on cord blood in three groups of neonates: 14 infected infants, 29 sero-reverted infants and 31 control neonates. No differences were observed between the three groups. At 3 months, IgG were significantly higher in the infected infants than in sero-reverted infants. After 6 months, CD4 + cell counts, CD4/CD8 ratio were significantly lower in the infected infants and serum IgG, IgA and IgM were significantly higher in the infected group. Antigenemia p24 was detected in 78% of the infected group before 6 months. Total HIV-specific antibody persisted and progressed after 6 months. These data and viral detection appear to be complementary and useful for therapeutic strategies.
