Five new F10 variants in hereditary factor x deficiency detected by high-throughput sequencing.
F10 gene
bleeding disorder
factor X deficiency
high throughput sequencing
Journal
Haemophilia : the official journal of the World Federation of Hemophilia
ISSN: 1365-2516
Titre abrégé: Haemophilia
Pays: England
ID NLM: 9442916
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
revised:
17
09
2023
received:
05
06
2023
accepted:
03
10
2023
medline:
14
11
2023
pubmed:
16
10
2023
entrez:
16
10
2023
Statut:
ppublish
Résumé
Factor X deficiency is a rare inherited bleeding disorder. To date, 181 variants are reported in the recently updated F10-gene variant database. This study aimed to describe new F10 variants. The F10 gene was analysed in 16 consecutive families with FX deficiency by a targeted high-throughput sequencing approach, including F10, F9, F8 genes, and 78 genes dedicated to haematological malignancies. We identified 19 variants (17 missense, one nonsense and one frameshift) and two copy number variations. Two patients presenting a combined FVII-FX deficiency showed a loss of one F10 gene copy (del13q34) associated with a missense variant on the remaining allele, leading to a FX:C significantly lower than the FVII:C level and explaining their unusual bleeding history. We reported five novel variants. Three missense variants (p.Glu22Val affecting the signal peptide cleavage site, p.Cys342Tyr removing the disulphide bond between the FX heavy and light chains, and p.Val385Met located in FX peptidase S1 domain) were detected at compound heterozygosis status in three patients with severe bleeding symptoms and FX:C level below 10 IU/dL. Two truncating variants p.Tyr279* and p.Thr434Aspfs*13 leading to an altered FX protein were found at heterozygous state in two patients with mild bleeding history. This study showed the feasibility and the interest of high-throughput sequencing approach for rare bleeding disorders, enabling the report of F10 gene screening in a 3-weeks delay, suitable for clinical use. The description of five new variants may contribute to a better understanding of the phenotype-genotype correlation in FX deficiency.
Substances chimiques
Factor X
9001-29-0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1565-1572Informations de copyright
© 2023 The Authors. Haemophilia published by John Wiley & Sons Ltd.
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