Original scientific paper
https://doi.org/10.3325/cmj.2022.63.166
Next-generation sequencing of von Willebrand factor and coagulation factor VIII genes: a cross-sectional study in Croatian adult patients diagnosed with von Willebrand disease
Ivana Lapić
orcid.org/0000-0002-0854-4526
; Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia
Margareta Radić Antolic
; Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia
Ana Boban
; Division of Hematology, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
Désirée Coen Herak
; Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia
Dunja Rogić
; Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia
Renata Zadro
; Medical Biochemistry Laboratory, St Catherine Specialty Hospital, Zagreb, Croatia
Abstract
Aim To identify the von Willebrand factor (VWF) gene variant status in Croatian adult patients diagnosed with von
Willebrand disease (VWD), provide differential diagnosis of
VWD subtypes, and identify patients with mild hemophilia
A (HA) who were earlier misdiagnosed as VWD.
Methods Coagulation testing included determination of
VWF gain-of-function mutant glycoprotein Ib binding activity (VWF:GPIbM), VWF antigen, VWF collagen-binding
activity, and multimeric analysis. Genetic analysis of VWF
and FVIII genes was performed with next-generation sequencing (NGS).
Results The study enrolled 50 patients (72% women; median age 37 years, range 18-75) from 44 unrelated families.
Fourteen patients were heterozygous for VWF gene variants compatible with type-1 VWD. Twelve had variants
associated with type 2, of whom seven were classified as
type 2A, four as type 2B, and one as type 2N. Six type-3
VWD patients were either homozygotes for null variants or
combined heterozygotes. Eleven variants within the VWF
gene were novel. Three female patients had variants within the FVIII gene, and were re-classified as mild-HA carriers, of whom one had causative novel variants both within
VWF and FVIII genes. Fifteen patients remained without a
defined genetic cause of their disorder, of whom five had
VWF:GPIbM levels below 50%.
Conclusion Croatian adult patients with VWD have considerable genetic heterogeneity. NGS of both VWF and
FVIII genes provided accurate differential diagnosis of VWD
subtypes and distinction of VWD from mild HA
Keywords
Hrčak ID:
279012
URI
Publication date:
21.4.2022.
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