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Understanding the haemophilias through molecular biology
SATELLITESYMPOSIUM Sunday June 24 1990
9 Understanding the haemophilias through molecular biology PE4KEI University of Wales College of Medicine, Card@ UK The cloning of the genes for factor VIII and factor IX has
allowed for the detailed analysis of these genes in patients with haemophilia A and B and the identification of DNA polymorphisms has resulted in accurate carrier detection and prenatal diagnosis in informative cases. In haemophilia A deletions of the factor VIII gene (either partial or total) have been detected in some 5% of severe patients some of whom have developed inhibitors to factor VIII. However, unlike in haemophilia B (see below) there is no apparent correlation between the size or location of the deletion and the presence or absence of an inhibitor. Ll sequence insertions have also been reported within exon 14 of the factor VIII gene. Point mutations have been identified within the
10 AIDS and hemophilia, 1990 BRETTLER DB Medical Center of Central MA - Memorial, Worcester, MA, USA As of March, 1990, over 1.200 U.S. hemophiliacs have
developed AIDS. 108 of these are in the pediatric age group (s: 13 years). Presenting symptoms of AIDS in hemophiliacs continue to be opportunistic infections (01) with Kaposi’s sarcoma being rare. It is estimated that 70% of American hemophiliacs are HIV seropositive with this percentage varying from 3050% internationally, depending on source of plasma used and average amount of concentrate infused. It currently appears that most patients that are seropositive, will develop an HIV related illness (AIDS). The timing of this depends on the length of the latency period. In a large study of seropositive hemophiliacs, the cumulative incidence rate of AIDS after 9 years of HIV-l infection was Fibrinolysis (1990) 4, supp.I, 4-5 0 Lon@nan Group UK Ltd ,990
factor VIII gene which give rise to both severe, moderate, or mild haemophilia A, many of which involve the CpG mutational hotspot where a C - T transition is seen. In addition mutations resulting in amino acid changes at thrombin cleavage sites within the molecular have also been observed, resulting in the CRM + phenotype. In haemophilia B factor IX gene deletions result in a high risk of inhibitor development and recently polymerase chain reaction (PRC) technology has resulted in a large number of point mutations-/small deletions being detected both at sites coding for known functional domains or sequences within the factor IX molecular, and at sites with no known function at present.
25.1%. It also appears that age at time of seroconversion may effect progression to AIDS. Patients that were infected at a younger age have a longer latency period. Treatment in the last year has significantly changed. Antiretroviral and 01 prophylaxis regimens based on CD4 cell levels have been instituted and may change the natural history of the disease.
9 Understanding the haemophilias through molecular biology PE4KEI University of Wales College of Medicine, Card@ UK The cloning of the genes for factor VIII and factor IX has
allowed for the detailed analysis of these genes in patients with haemophilia A and B and the identification of DNA polymorphisms has resulted in accurate carrier detection and prenatal diagnosis in informative cases. In haemophilia A deletions of the factor VIII gene (either partial or total) have been detected in some 5% of severe patients some of whom have developed inhibitors to factor VIII. However, unlike in haemophilia B (see below) there is no apparent correlation between the size or location of the deletion and the presence or absence of an inhibitor. Ll sequence insertions have also been reported within exon 14 of the factor VIII gene. Point mutations have been identified within the
10 AIDS and hemophilia, 1990 BRETTLER DB Medical Center of Central MA - Memorial, Worcester, MA, USA As of March, 1990, over 1.200 U.S. hemophiliacs have
developed AIDS. 108 of these are in the pediatric age group (s: 13 years). Presenting symptoms of AIDS in hemophiliacs continue to be opportunistic infections (01) with Kaposi’s sarcoma being rare. It is estimated that 70% of American hemophiliacs are HIV seropositive with this percentage varying from 3050% internationally, depending on source of plasma used and average amount of concentrate infused. It currently appears that most patients that are seropositive, will develop an HIV related illness (AIDS). The timing of this depends on the length of the latency period. In a large study of seropositive hemophiliacs, the cumulative incidence rate of AIDS after 9 years of HIV-l infection was Fibrinolysis (1990) 4, supp.I, 4-5 0 Lon@nan Group UK Ltd ,990
factor VIII gene which give rise to both severe, moderate, or mild haemophilia A, many of which involve the CpG mutational hotspot where a C - T transition is seen. In addition mutations resulting in amino acid changes at thrombin cleavage sites within the molecular have also been observed, resulting in the CRM + phenotype. In haemophilia B factor IX gene deletions result in a high risk of inhibitor development and recently polymerase chain reaction (PRC) technology has resulted in a large number of point mutations-/small deletions being detected both at sites coding for known functional domains or sequences within the factor IX molecular, and at sites with no known function at present.
25.1%. It also appears that age at time of seroconversion may effect progression to AIDS. Patients that were infected at a younger age have a longer latency period. Treatment in the last year has significantly changed. Antiretroviral and 01 prophylaxis regimens based on CD4 cell levels have been instituted and may change the natural history of the disease.