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

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cam.issuedOnline2018-09-26
dc.contributor.authorGao, Jiali
dc.contributor.authorBrackley, Simon
dc.contributor.authorMann, J
dc.contributor.orcidMann, Jake [0000-0002-4711-9215]
dc.date.accessioned2018-11-17T00:31:00Z
dc.date.available2018-11-17T00:31:00Z
dc.date.issued2019-05
dc.description.abstractPurpose: 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.
dc.identifier.doi10.17863/CAM.27489
dc.identifier.eissn1530-0366
dc.identifier.issn1098-3600
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285352
dc.language.isoeng
dc.publisherSpringer Nature
dc.publisher.urlhttp://dx.doi.org/10.1038/s41436-018-0309-9
dc.subjectATP7B
dc.subjectWilson disease
dc.subjectdatabase
dc.subjectpathogenic variants
dc.subjectprevalence
dc.subjectAlleles
dc.subjectCopper-Transporting ATPases
dc.subjectDNA Mutational Analysis
dc.subjectDatabases, Genetic
dc.subjectGene Frequency
dc.subjectGenetic Variation
dc.subjectGenotype
dc.subjectHepatolenticular Degeneration
dc.subjectHigh-Throughput Nucleotide Sequencing
dc.subjectHumans
dc.subjectMutation
dc.subjectPrevalence
dc.titleThe global prevalence of Wilson’s Disease from next generation sequencing data
dc.typeArticle
dcterms.dateAccepted2018-09-05
prism.publicationNameGenetics in Medicine
rioxxterms.licenseref.startdate2018-09-05
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1038/s41436-018-0309-9

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