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Haemophilia
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Haemophilia
Article . 2008 . Peer-reviewed
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Haemophilia
Article . 2009
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The spectrum of the factor 8 (F8) defects in Taiwanese patients with haemophilia A

Authors: G-C, Ma; S-P, Chang; M, Chen; S-J, Kuo; C-S, Chang; M-C, Shen;

The spectrum of the factor 8 (F8) defects in Taiwanese patients with haemophilia A

Abstract

Summary.  Haemophilia A (HA) is an X‐linked recessive bleeding disorder caused by various types of pathological defects in the factor VIII gene (F8), which encodes coagulation factor VIII (FVIII). To date, several studies on the spectra of F8 defects have been performed in Western populations, but similar studies in Asian races are scarce. Here, we report the distribution of the mutations within the F8 gene in 31 Taiwanese unrelated HA patients (19 severe and 10 moderate/mild males and two severe females). Of these, 12 (38.7%) and one (3.2%) severe males were genotyped with the recurrent IVS22 and IVS1 inversion, respectively, similar to that in general populations (IVS22: 40–50%; IVS1: 2–5%). The F8 defects in the remaining 18 inversion‐negative patients cover a wide spectrum, in which 17 different mutations were identified (10 missense and three nonsense mutations, and two small and two large deletions). Eleven of these mutations are novel: seven caused missense substitutions and four resulted in truncated proteins. To assess the putative pathogenetic impacts of the newly amino acid substitutions, computer analyses were performed based on molecular 3D modelling. The degree of conservation in cross‐species FVIIIs and the position in known functional FVIII regions were studied. The novel missense mutations found in our series all occurred at evolutionary conserved residues that may carry a functional importance in our analyses. The results of this study add the short list of Taiwanese/Chinese F8 mutations, and will enhance our understanding of the molecular basis of FVIII function and the mechanism underlying HA.

Keywords

Male, Factor VIII, Genotype, DNA Mutational Analysis, Mutation, Missense, Hemophilia A, Cohort Studies, Phenotype, Asian People, Codon, Nonsense, Humans, Female, Gene Deletion

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
22
Top 10%
Top 10%
Average
bronze