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Investigating common mutations in ATP7B gene and the prevalence of Wilson’s disease in the Thai population using population-based genome-wide datasets

Journal of Human Genetics (2024)Cite this article

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Abstract

Wilson’s disease (WD) is a rare metabolic disorder caused by variations in the ATP7B gene. It usually manifests hepatic, neurologic, and psychiatric symptoms due to excessive copper accumulation. The prevalence of WD and its common variants differ across populations. This study aimed to examine these aspects of WD within the Thai population, where information has been limited. We reviewed ClinVar and the Wilson Disease Mutation Database, organizing variants classified as pathogenic or likely pathogenic in one or both databases as “relaxed” and “strict” lists. Allele frequencies were estimated from genotyping array data (Asian Screening Array: ASA; Illumina Corp, CA) of 6291 Thai subjects, which also underwent genotype imputation. The prevalence of WD in the Thai population was estimated assuming Hardy-Weinberg Equilibrium. The strict list yielded a prevalence of 1/24,128 (carrier frequency=1/78), while the relaxed list yielded a prevalence of 1/9971 (carrier frequency=1/50). The most common WD variants in Thai subjects were c.2333 G > T, c.3443 T > C, and c.813 C > A from the strict list, and c.3316 G > A and c.2605 G > A from the relaxed list. The ASA chip covered approximately 59 and 24% of WD variants from the strict and relaxed lists, respectively. Based on the estimated prevalence, a carrier screening program for WD is not currently required in Thailand. However, as genotyping services become more affordable and accessible, such a program would facilitate early identification, treatment, and prevention of WD.

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Data availability

At the moment, the ASA data set is available upon request from the corresponding author (jakrise@gmail.com). We plan to deposit the data on the National Science and Technology Development Agency (NSTDA) website under the Genomics Thailand programme in the future.

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Acknowledgements

The original SNP array assay was jointly funded by Faculty of Medicine Ramathibodi Hospital and the Department of Medical Sciences, Ministry of Public Health, Thailand. NGS was funded by the Health Systems Research Institute of Thailand through Mahidol University. The authors are thankful to the Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, especially Ms. Aruchalean Taweewongsounton, Ms. Supranee Thongpradit, and Ms. Preeyaporn Wichakong for performing the SNP array assay. We would like to express our gratitude to Dr. Wasun Chantratita and the Center for Medical Genomics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, for providing the facilities for NGS processing and analysis. We greatly appreciate Ms. Nartthawee Thongchompoo for carrying out the NGS work and Mr. Sommon Klumsathian for his helpful advice for doing NGS data analysis. Finally, we thank the staff of both facilities, as well as professors and friends from the Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, for their ongoing support.

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Authors and Affiliations

  1. Program in Translational Medicine, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samutprakarn, Thailand

    Paravee Own-eium & Donniphat Dejsuphong

  2. Division of Cardiology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Prin Vathesatogkit

  3. Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Piyamitr Sritara

  4. Division of Medical Genetics and Molecular Medicine, Department of Internal Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Thanyachai Sura

  5. Department of Community Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Wichai Aekplakorn & Jakris Eu-ahsunthornwattana

  6. Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

    Bhoom Suktitipat

  7. Integrative Computational BioScience (ICBS) Center, Mahidol University, Nakhon Pathom, Thailand

    Bhoom Suktitipat

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Own-eium, P., Dejsuphong, D., Vathesatogkit, P. et al. Investigating common mutations in ATP7B gene and the prevalence of Wilson’s disease in the Thai population using population-based genome-wide datasets. J Hum Genet (2024). https://doi.org/10.1038/s10038-024-01292-z

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