| 1. |
- Antonarakis, S. E., et al.
(författare)
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Factor VIII gene inversions in severe hemophilia A : Results of an international consortium study
- 1995
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 86:6, s. 2206-2212
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Tidskriftsartikel (refereegranskat)abstract
- Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells ware observed among 225 cases (≃ 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).
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| 2. |
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| 3. |
- Lee, C A, et al.
(författare)
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Prophylactic treatment in Sweden - Overtreatment or optimal model?
- 1998
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 4:4, s. 409-412
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Tidskriftsartikel (refereegranskat)abstract
- At the haemophilia centre in Malmo, Sweden, regular prophylactic treatment is begun at 1-1 1/4 years of age, before the onset of joint bleeds. The dose and dose interval are optimised by means of pharmacokinetic studies to determine the individual patient's FVIII or IX metabolism, the goal of maintaining a level > 1% of normal being taken as a guideline which experience has shown to yield satisfactory control of bleeding diathesis. An optimal model for prophylactic treatment needs to be applicable to haemophiliacs and acceptable to health authorities in a majority of the countries in the world. To fulfill these criteria, the Swedish model, which has been shown to yield most satisfactory outcome, can hopefully be further refined in the future. Were continuous infusion, using a recombinate concentrate with a prolonged half-life, technically feasible and socially acceptable to the child, we would probably have attained the optimal model of prophylactic treatment.
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| 4. |
- Ljung, R. C R
(författare)
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Gene mutations and inhibitor formation in patients with hemophilia B
- 1995
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Ingår i: Acta Haematologica. - : S. Karger AG. - 0001-5792 .- 1421-9662. ; 94:SUPPL. 1, s. 49-52
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Tidskriftsartikel (refereegranskat)abstract
- The nature of the mutation in the factor IX gene is an important factor in determining whether a patient with hemophilia B will develop an inhibitor. In a series of 62 Swedish families with hemophilia B, including 30 with the severe form, approximately one third of the families exhibiting deletions or nonsense mutations contained one member who developed an inhibitor. The risk for inhibitor development in family members carrying missense mutations was virtually zero.
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| 5. |
- Ljung, R. C R, et al.
(författare)
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Origin of mutation in sporadic cases of haemophilia A
- 1999
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 106:4, s. 870-874
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to define the origin of mutation in sporadic cases of severe haemophilia A. The series was composed of 31 families with sporadic severe haemophilia A in the geographical catchment area of the Malmo haemophilia centre. The mutation was characterized in 29/31 families: inversion type 1 (n = 11), inversion type 2 (n = 3), other inversion (n= 1), small or partial deletion (n = 6), insertion (n = 2), non-sense mutation (n = 4) and mis-sense mutation (n = 2). Of 29 probands, eight carried a de novo mutation, whereas the proband's mother was found to carry the mutation in 21/29 families. Of the 21 carrier mothers, 16 had de novo mutations (i.e. the proband's maternal grandfather and grandmother were non-carriers). Owing to the lack of samples from the grandparents, origin could not be determined in the remaining five families. Polymorphisms of the FVIII gene were used to determine whether the de novo mutation of the carrier mother was of paternal or maternal origin. In 15/16 cases the mutation was of paternal origin and in 1/16 cases of maternal origin. In the series as a whole, mutation frequency was 6-fold higher in males than in females, but no differences in the ratio of sex-specific mutations rates was found among different types of mutation.
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| 6. |
- Ljung, R.C.R.
(författare)
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Prenatal diagnosis of haemophilia
- 1999
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 5:2, s. 84-87
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Forskningsöversikt (refereegranskat)abstract
- Genotype assessment based on direct identification of the pathogenic mutation in a chorionic villi sample obtained in the 11-12th gestational week is the most reliable method for prenatal diagnosis and should be used if available. Genetic linkage studies of polymorphisms should be the second choice in the assessment of carriers and in prenatal diagnosis. Carriers of haemophilia should be offered adequate psychosocial support before, during and after the prenatal diagnostic procedures.
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| 7. |
- Ljung, R. C.R.
(författare)
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Prenatal diagnosis of haemophilia
- 1996
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Ingår i: Bailliere's Clinical Haematology. - 0950-3536. ; 9:2, s. 243-257
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Tidskriftsartikel (refereegranskat)abstract
- Prenatal diagnosis of haemophilia A or B is possible by means of chorionic villus biopsy in the first trimester which traces the mutation or informative genetic markers. If possible, direct gene analysis of the mutation is preferred, The natural starting point in haemophilia A is to ascertain whether the disease is due to inversion in the X-chromosome, which is the case in almost half of the severe cases, In haemophilia B, most families carry a unique mutation which needs to be characterized, In the immediate future, much of the prenatal diagnosis will be based on indirect genetic markers, repeats or polymorphisms, of the F.VIII and IX genes, Today chorionic villus sampling is the most widely used method but amniotic fluid, fetal blood and pre-implantation genetic diagnostics can also be used in selected cases, Prenatal diagnosis must be preceded by adequate genetic counselling and risk assessment of the potential carrier and subsequent support during the diagnostic process.
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| 8. |
- Ljung, R. C R
(författare)
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Prophylactic infusion regimens in the management of hemophilia
- 1999
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 82:2, s. 525-530
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Tidskriftsartikel (refereegranskat)abstract
- To summarize, prophylactic treatment of hemophilia begun at an early age has been gaining acceptance as the optimal therapeutic option in an increasing number of hemophilia centers in the developed world in recent years. In all too many parts of the world, however, this option must be viewed as a long-range goal in hemophilia care, since national economic resources are insufficient for regular prophylactic treatment to be feasible at the moment. The future development of prophylaxis seems to be focused on three different areas. First, research has focused on improving the cost-effectiveness of the current model by testing daily, frequent injections using novel devices for venous access or continuous infusion with portable or implantable mini-pumps and administration of bioengineered concentrates with a prolonged half-life at a reduced price. Secondly, a breakthrough in gene therapy, which will enable us to introduce a gene producing an amount of clotting factor sufficient to provide a continuous prophylactic concentration in the blood. Finally, the most mind-challenging option makes most of the discussion in this chapter obsolete and focuses on the development of an oral compound, peptide, or peptidomimetic agent with the capacity to activate the coagulation cascade in a controllable way.
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| 9. |
- Ljung, R. C R
(författare)
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Venous Access in Children with Inhibitors
- 2008
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Ingår i: Inhibitors in Patients with Haemophilia. - Oxford, UK : Blackwell Science Ltd. - 0632064773 - 9780632064779 - 9780470757260 ; , s. 36-41
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Bokkapitel (refereegranskat)
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