The global prevalence of Wilson’s Disease from next generation sequencing data

Gao, Jiali 
Brackley, Simon 

Change log

Purpose: Wilson Disease (WD) is an autosomal recessive disorder of copper metabolism, caused by mutations in ATP7B. We aimed to: 1) perform a meta-analysis of previous WD prevalence estimates, 2) estimate the prevalence of WD from population sequencing data, and 3) generate an ATP7B gene variant database. Methods: MEDLINE and EMBASE were systematically searched. Previous prevalence estimates were subjected to meta-analysis. All previously reported pathogenic ATP7B variants were compiled and annotated with GnomAD allele frequencies. Pooled global and ethnicity-specific genetic prevalences for WD were generated using the Hardy-Weinberg equation. Results: Meta-analysis of genetic studies of WD prevalence gave an estimate 12.7 per 100,000 (95% CI: 6.3-23.0). We developed a referenced, searchable ATP7B database comprising 11,520 variants including 782 previously reported disease variants, which can be found at 216/782 of these were present in GnomAD, remained after filtering by allele frequency and met American College of Medical Genetics criteria. Based on these, the genetic prevalence of WD was 13.9 per 100,000 (95% CI: 12.9-14.9), or 1 per 7,194. Combining this with 60 predicted pathogenic variants gave a birth prevalence of 15.4 per 100,000 (95% CI: 14.4- 16.5). Conclusion: The genetic prevalence of Wilson disease may be greater than previous estimates.

Publication Date
Online Publication Date
Acceptance Date
ATP7B, Wilson disease, database, pathogenic variants, prevalence, Alleles, Copper-Transporting ATPases, DNA Mutational Analysis, Databases, Genetic, Gene Frequency, Genetic Variation, Genotype, Hepatolenticular Degeneration, High-Throughput Nucleotide Sequencing, Humans, Mutation, Prevalence
Journal Title
Genetics in Medicine
Journal ISSN
Volume Title
Springer Nature