Most factor VIII B domain missense mutations are unlikely to be causative mutations for severe hemophilia A: implications for genotyping.

ABSTRACT:

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Background & objective

 The factor VIII (FVIII) B domain shares very little amino acid homology with other known proteins and is not directly necessary for procoagulant activity. Despite this, missense mutations within the B domain have been reported in patients with hemophilia A. Given that the B domain is dispensable for secretion and function of FVIII, we hypothesized that these mutations should not be causative of hemophilia A in these patients.

Methods

 Plasmid vectors containing B domain missense mutations that were reported to be associated with moderate/severe hemophilia A (T751S, D826E, V993L, H1047Y, T1353A, N1441K, L1462P, E1579D, A1591S, P1641L and S1669L) were analyzed for their effect on synthesis and secretion compared with FVIII wild-type (

SUBMITTER: Ogata K 

PROVIDER: S-EPMC3111924 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature