Purpose
Wilson disease (WD) is an autosomal recessive disorder of copper metabolism, caused by pathogenic variants 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% confidence interval [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
http://www.wilsondisease.tk/
; 216/782 of these were present in gnomAD, remained after filtering by allele frequency, and met American College of Medical Genetics and Genomics criteria. Based on these, the genetic prevalence of WD was 13.9 per 100,000 (95% CI: 12.9–14.9), or 1 per 7194. Combining this with 60 predicted pathogenic variants gave a birth prevalence of 15....

The global prevalence of Wilson disease from next-generation sequencing data

10.1038/s41436-018-0309-9