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Original research
Genetic variations of type 2 and type 3 von Willebrand diseases in Thailand
  1. Supanun Lauhasurayotin1,2,
  2. Chatphatai Moonla3,4,
  3. Rungnapa Ittiwut5,6,
  4. Chupong Ittiwut5,6,
  5. Natsaruth Songthawee7,
  6. Patcharee Komvilaisak8,
  7. Rungrote Natesirinilkul9,
  8. Nongnuch Sirachainan10,
  9. Ponlapat Rojnuckarin3,4,
  10. Darintr Sosothikul1,2,
  11. Kanya Suphapeetiporn5,6
  1. 1 Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
  2. 2 Integrative and Innovative Hematology/Oncology Research Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  3. 3 Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
  4. 4 Center of Excellence in Translational Hematology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
  5. 5 Center of Excellence for Medical Genomics, Medical Genomics Cluster, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  6. 6 Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
  7. 7 Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
  8. 8 Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
  9. 9 Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
  10. 10 Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  1. Correspondence to Professor Darintr Sosothikul; dsosothikul{at}hotmail.com

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.

  • Genetic Diseases, Inborn
  • von Willebrand Diseases
  • Diagnostic Techniques and Procedures

Data availability statement

Data are available upon responable request. SL, CM and DS have full access to all the data and take responsibility for the integrity and accuracy of the data. The supporting data are available from the corresponding author.

https://doi.org/10.1136/jcp-2023-209123

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    Data availability statement

    Data are available upon responable request. SL, CM and DS have full access to all the data and take responsibility for the integrity and accuracy of the data. The supporting data are available from the corresponding author.

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    Footnotes

    • Handling editor Vikram Deshpande.

    • SL and CM contributed equally.

    • Contributors SL and CM designed the study, collected samples and clinical data, analysed data and wrote the first draft of the manuscript; RI and CI performed DNA extraction and PCR, analysed bioinformatic data and critically reviewed and wrote the manuscript; NSo, PK, RN and NSi collected samples and clinical data and critically reviewed and wrote the manuscript; PR and KS remarked on the WES results and critically reviewed and wrote the manuscript; DS conceptualised and designed the study, collected samples and clinical data, analysed data, critically reviewed and wrote the manuscript and was responsible for the overall content as the guarantor; and all authors revised and approved the final version of the manuscript.

    • Funding This research was supported by the Thai Society of Hematology and the Fundamental Fund, Thailand Science Research and Innovation (grant no. 4390675).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.