1. Molecular Characterization of Two Homozygous Factor VII Variants Associated with Intracranial Bleeding
- Author
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Maria Eugenia Chollet, Heidi Glosli, Paul Hoff Backe, Bernd Thiede, Elisabeth Andersen, Nina Iversen, Carola E. Henriksson, Benedicte Stavik, Marit Sletten, and Ellen Skarpen
- Subjects
Models, Molecular ,Proband ,Arginine ,Mutation, Missense ,CHO Cells ,Factor VIIa ,030204 cardiovascular system & hematology ,Biology ,Frameshift mutation ,03 medical and health sciences ,Exon ,chemistry.chemical_compound ,Cricetulus ,0302 clinical medicine ,hemic and lymphatic diseases ,0502 economics and business ,Animals ,Humans ,Missense mutation ,Genetic Predisposition to Disease ,Age of Onset ,chemistry.chemical_classification ,Hemostasis ,Factor VII ,Coagulants ,Homozygote ,05 social sciences ,Exons ,Hematology ,Endoplasmic Reticulum Stress ,Molecular biology ,Recombinant Proteins ,Amino acid ,HEK293 Cells ,Phenotype ,Treatment Outcome ,Protein destabilization ,chemistry ,Codon, Nonsense ,050211 marketing ,Intracranial Hemorrhages - Abstract
Clinical parameters have been extensively studied in factor (F) VII deficiency, but the knowledge of molecular mechanisms of this disease is scarce. We report on three probands with intracranial bleeds at an early age, one of which had concomitant high titer of FVII inhibitor. The aim of the present study was to identify the causative mutations and to elucidate the underlying molecular mechanisms. All nine F7 exons were sequenced in the probands and the closest family members. A homozygous deletion in exon 1, leading to a frame shift and generation of a premature stop codon (p.C10Pfs*16), was found in proband 1. Probands 2 and 3 (siblings) were homozygous for a missense mutation in exon 8, resulting in a glycine (G) to arginine (R) substitution at amino acid 240 (p.G240R). All probands had severely reduced FVII activity (FVII:C
- Published
- 2021