The global prevalence of Wilson’s Disease from next generation sequencing data
Authors
Gao, Jiali
Brackley, Simon
Mann, J
Publication Date
2019-05Journal Title
Genetics in Medicine
ISSN
1098-3600
Publisher
Springer Nature
Type
Article
Metadata
Show full item recordCitation
Gao, J., Brackley, S., & Mann, J. (2019). The global prevalence of Wilson’s Disease from next generation sequencing data. Genetics in Medicine https://doi.org/10.1038/s41436-018-0309-9
Abstract
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
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 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.
Keywords
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
Identifiers
External DOI: https://doi.org/10.1038/s41436-018-0309-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285352
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