Factor VIII gene inversions in severe hemophilia a patients

Water, Neil S. Van De; Williams, Ruth; Nelson, Jan; Browett, Peter

doi:10.1080/00313029500169542

Cited by 6 publications

(3 citation statements)

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“…Sixty‐one per cent of the patients were shown to have an inversion of intron 22 of the FVIII gene. This proportion is higher than would have been expected, as most published studies have documented this abnormality in approximately 45% of patients with severe haemophilia A [3]. Three of the four subjects who developed inhibitors were shown to have gene inversions or large deletions of the FVIII gene, which are known to be associated with an increased risk of inhibitor development [4].…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of KOGENATE^® Bayer in previously untreated patients (PUPs) and minimally treated patients (MTPs)

Giangrande

2002

Haemophilia

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Safety and efficacy of KOGENATE Bayer (Kogenate FS), a second-generation full-length recombinant factor VIII formulated with sucrose as stabilizer and produced without the addition of human albumin during purification and the final formulation, was assessed in a prospective, international clinical trial including 31 previously untreated patients (PUPs) and minimally treated patients (MTPs) with severe haemophilia A in home therapy and surgery. Factor VIII inhibitor development was monitored and mutation type profiles were analysed. As of 30 June 2000, the patients received a total of 2.729 infusions (mean 88; range 6-274) for bleeding episodes, surgery or prophylactic treatment. No unexpected drug-related adverse events were observed. Four patients developed an inhibitor after 3-12 exposure days (EDs). One patient successfully underwent immune tolerance treatment; inhibitors in two patients disappeared spontaneously with on-demand treatment, while the inhibitor titre remains low in one patient. Twenty-nine patients (93%) with more than 20 EDs can be regarded as at low risk for inhibitor development. In conclusion, KOGENATE Bayer is efficacious and well-tolerated for treatment of children with severe haemophilia A. The incidence of inhibitor formation is not different to that observed with other recombinant or plasma-derived products.

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Section: Discussionmentioning

confidence: 99%

Safety and efficacy of KOGENATE^® Bayer in previously untreated patients (PUPs) and minimally treated patients (MTPs)

Giangrande

2002

Haemophilia

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“…Haemophilia A displays a wide range of clinical severity resulting from a diverse heterogeneity of defects within the factor VIII gene. Except for a common inversion in 10-20% of all cases and 45% of severe cases, most defects are due to single point mutations (1,2). Large deletions, greater than 1 kb, are responsible for approximately 5% of severe haemophilia cases.…”

Section: Introductionmentioning

confidence: 99%

A 20.7 kb Deletion within the Factor VIII Gene Associated with LINE-1 Element Insertion

Water¹,

Williams²,

Ockelford³

et al. 1998

Thromb Haemost

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SummaryLarge deletions within the factor VIII gene account for approximately 5% of the mutations causing haemophilia A. The characterization of such mutations can provide insights into the molecular mechanisms of these and other deletions in man. We have analyzed a 20.7 kb deletion spanning exons 15 to 20 within the factor VIII gene in a patient with severe haemophilia A. Long range PCR was used to investigate the extent of the deletion and to provide a template for sequencing across the deletion breakpoint. A 38-base insertion homologous to the 3’ region of a LINE-1 (L1) element was detected at the breakpoint of the deletion. Normal sequence at the 5’ breakpoint in intron 14 was homologous to an L1 flanking region and normal sequence at the 3’ breakpoint in intron 20 was homologous to an adjacent sequence within the same L1 flanking region. A molecular mechanism for the deletion involving retrotransposition of a readthrough product of an L1 element plus its 3’ flanking region is suggested.

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“…Hemophilia B caused by genetic defects occur in the coagulation FIX; the FIX deficiency will inhibit the activation of FX by FVIIa through external coagulation pathway (Furie et al, 1994;Thompson, 1986). About half The patients who suffer from severe hemophilia A there is a large inversion in intron 22 of their FVIII mRNA ( Figure 2) which it is repeated (Arruda et al, 1995;Deutz-Terlouw et al, 1995;Okamoto et al, 1995;Pieneman et al, 1995;Van de Water et al, 1995;Goodeve et al, Jenkins et al, 1994;Naylor et al, 1993;Naylor et al, 1992). Different alleles of the VNTR (di nucleotides) have observed in intron 13 of FVIII in people with hemophilia A (Kochhan et al, 1994).…”

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confidence: 99%

Using Factor VII in Hemophilia Gene Therapy

Kazemi¹

2011

Targets in Gene Therapy

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Factor VIII gene inversions in severe hemophilia a patients

Cited by 6 publications

References 10 publications

Safety and efficacy of KOGENATE^® Bayer in previously untreated patients (PUPs) and minimally treated patients (MTPs)

Safety and efficacy of KOGENATE^® Bayer in previously untreated patients (PUPs) and minimally treated patients (MTPs)

A 20.7 kb Deletion within the Factor VIII Gene Associated with LINE-1 Element Insertion

Using Factor VII in Hemophilia Gene Therapy

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Factor VIII gene inversions in severe hemophilia a patients

Cited by 6 publications

References 10 publications

Safety and efficacy of KOGENATE® Bayer in previously untreated patients (PUPs) and minimally treated patients (MTPs)

Safety and efficacy of KOGENATE® Bayer in previously untreated patients (PUPs) and minimally treated patients (MTPs)

A 20.7 kb Deletion within the Factor VIII Gene Associated with LINE-1 Element Insertion

Using Factor VII in Hemophilia Gene Therapy

Contact Info

Product

Resources

About

Safety and efficacy of KOGENATE^® Bayer in previously untreated patients (PUPs) and minimally treated patients (MTPs)

Safety and efficacy of KOGENATE^® Bayer in previously untreated patients (PUPs) and minimally treated patients (MTPs)