Genetic variations of type 2 and type 3 von Willebrand diseases in Thailand
2
Issued Date
2023-01-01
Resource Type
ISSN
00219746
eISSN
14724146
Scopus ID
2-s2.0-85178389458
Journal Title
Journal of Clinical Pathology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Clinical Pathology (2023)
Suggested Citation
Lauhasurayotin S., Moonla C., Ittiwut R., Ittiwut C., Songthawee N., Komvilaisak P., Natesirinilkul R., Sirachainan N., Rojnuckarin P., Sosothikul D., Suphapeetiporn K. Genetic variations of type 2 and type 3 von Willebrand diseases in Thailand. Journal of Clinical Pathology (2023). doi:10.1136/jcp-2023-209123 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/91421
Title
Genetic variations of type 2 and type 3 von Willebrand diseases in Thailand
Other Contributor(s)
Abstract
Aims: Von Willebrand disease (VWD) is an inherited haemostatic disorder with a wide range of bleeding phenotypes based on von Willebrand factor (VWF) levels. Multiple assays including VWF gene analysis are employed to correctly diagnose VWD and its subtypes. However, data on VWF mutations among Southeast Asian populations are lacking. We, therefore, aimed to explore genetic variations in Thai patients with type 2 and type 3 VWD by whole exome sequencing (WES). Methods: In this multicentre study, Thai patients with type 2 and type 3 VWD, according to the definitions and VWF levels recommended by the international guidelines, were recruited. WES was performed using DNA extracted from peripheral blood in all cases. The novel variants were verified by Sanger sequencing. Results: Fifteen patients (73% females; median age at diagnosis 3.0 years) with type 2 (n=12) and type 3 VWD (n=3) from 14 families were enrolled. All patients harboured at least one VWF variant. Six missense (p.Arg1374Cys, p.Arg1374His, p.Arg1399Cys, p.Arg1597Trp, p.Ser1613Pro, p.Pro1648Arg) and one splice-site (c.3379+1G>A) variants in the VWF gene were formerly described. Notably, six VWF variants, including three missense (p.Met814Ile, p.Trp856Cys, p.Pro2032Leu), one deletion (c.2251delG) and two splice-site (c.7729+4A>C, c.8115+2delT) mutations were novelly identified. Compound heterozygosity contributed to type 2 and type 3 VWD phenotypes in two and one patients, respectively. Conclusions: Type 2 and type 3 VWD in Thailand demonstrate the mutational variations among VWF exons/introns with several unique variants. The WES-based approach potentially provides helpful information to verify VWD diagnosis and facilitate genetic counselling in clinical practice.