Genetic analysis of non-severe hemophilia A phenotype with A discrepancy between one-stage and chromogenic factor VIII activity assays.
Transfus Apher Sci
; 60(5): 103194, 2021 Oct.
Article
em En
| MEDLINE
| ID: mdl-34275734
ABSTRACT
INTRODUCTION:
The diagnosis of hemophilia A (HA) is based on the measurement of factor VIII activity (VIIIC). About one-third of non-severe HA patients show a discrepancy of VIIIC measured by one-stage (VIIIC 1st) and chromogenic (VIIIC chr) assays. Different mutations in the F8 gene may cause the discrepancy in results of the FVIII activity assay. The aim of this study was to investigate F8 gene mutations in patients with assay discrepancies and to evaluate their impact on the results of VIIIC assays.METHODS:
Mutation analysis was performed on 41 individuals with a discrepancy in VIIIC 1st and FVIII C chr assays by direct sequencing. In addition, the effect of the variants on FVIII macromolecule structure was investigated by in silico and bioinformatics tools.RESULTS:
Genetic analysis disclosed 22 different variants, of which 19 were identified for the first time to be involved in the phenotype of VIIIC discrepancy. Most of the variants related to the higher VIIIC 1st were found in A1, A2, A3 domains. The variant related to VIIIC chr > VIIIC 1st was located in the thrombin cleavage site. In silico analysis showed the effect of variants on FVIII macromolecule stability, which may be the possible mechanism causing the discrepancy.CONCLUSION:
Our data shed light on the impact of genetic defects on VIIIC assay and provided evidence that the consideration of these mutations may open a new window to the proper diagnosis and treatment monitoring of non-severe HA patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator VIII
/
Hemofilia A
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Transfus Apher Sci
Ano de publicação:
2021
Tipo de documento:
Article