{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T22:45:48Z","timestamp":1794523548166,"version":"4.9.1"},"reference-count":26,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2022,7,15]]},"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Fabry disease is an X-linked lysosomal storage disorder resulting from deficiency of the alpha-galactosidase A enzyme leading to accumulation of globotriaosylceramide in multiple organ sites with prominent cardiovascular and renal involvement. Global prevalence estimates of Fabry disease based on clinical ascertainment range from 1 in 40\u2009000 to 1 in 170\u2009000. We aimed to determine the prevalence of Fabry disease-causing variants in UK Biobank.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We sought <jats:italic>GLA<\/jats:italic> gene variants in exome sequencing data from 200\u2009643 individuals from UK Biobank. We used ACMG\/AMP guidelines (American College of Medical Genetics\/Association for Molecular Pathology) to classify pathogenicity and compared baseline biomarker data, hospital ICD-10 (International Classification of Diseases version-10) codes, general practitioner records and self-reported health data with those without pathogenic variants.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified 81 <jats:italic>GLA<\/jats:italic> coding variants. We identified eight likely pathogenic variants on the basis of being rare (&lt;1\/10 000 individuals) and either previously reported to cause Fabry disease, or being protein-truncating variants. Thirty-six individuals carried one of these variants. In the UK Biobank, the prevalence of likely pathogenic Fabry disease-causing variants is 1\/5732 for late-onset disease-causing variants and 1\/200 643 for variants causing classic Fabry disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Fabry disease-causing <jats:italic>GLA<\/jats:italic> variants are more prevalent in an unselected population sample than the reported prevalence of Fabry disease. These are overwhelmingly variants associated with later onset. It is possible the prevalence of later-onset Fabry disease exceeds current estimates.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2022-108523","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T13:20:22Z","timestamp":1660742422000},"page":"391-396","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":56,"title":["Prevalence of Fabry disease-causing variants in the UK Biobank"],"prefix":"10.1136","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0284-6048","authenticated-orcid":false,"given":"Mark","family":"Gilchrist","sequence":"first","affiliation":[{"name":"College of Medicine and Health, University of Exeter Medical School, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Casanova","sequence":"additional","affiliation":[{"name":"College of Medicine and Health, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9256-6065","authenticated-orcid":false,"given":"Jess S","family":"Tyrrell","sequence":"additional","affiliation":[{"name":"College of Medicine and Health, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5108-7615","authenticated-orcid":false,"given":"Stuart","family":"Cannon","sequence":"additional","affiliation":[{"name":"College of Medicine and Health, University of Exeter Medical School, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R","family":"Wood","sequence":"additional","affiliation":[{"name":"Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Fife","sequence":"additional","affiliation":[{"name":"College of Medicine and Health, University of Exeter Medical School, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2570-3864","authenticated-orcid":false,"given":"Katherine","family":"Young","sequence":"additional","affiliation":[{"name":"College of Medicine and Health, University of Exeter Medical School, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A","family":"Oram","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael N","family":"Weedon","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,8,17]]},"reference":[{"key":"2025101712554073000_60.4.391.1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-30"},{"key":"2025101712554073000_60.4.391.2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.4.e38"},{"key":"2025101712554073000_60.4.391.3","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.11.769"},{"key":"2025101712554073000_60.4.391.4","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0253-6"},{"key":"2025101712554073000_60.4.391.5","doi-asserted-by":"publisher","DOI":"10.1086\/504601"},{"key":"2025101712554073000_60.4.391.6","article-title":"Newborn screening for Fabry disease in the Western region of Japan","volume":"22","author":"Sawada","year":"2020","journal-title":"Mol Genet Metab Rep"},{"key":"2025101712554073000_60.4.391.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.06.048"},{"key":"2025101712554073000_60.4.391.8","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21074"},{"key":"2025101712554073000_60.4.391.9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ymgme.2020.04.006","article-title":"A comprehensive testing algorithm for the diagnosis of Fabry disease in males and females","volume":"130","author":"Stiles","year":"2020","journal-title":"Mol Genet Metab"},{"key":"2025101712554073000_60.4.391.10","article-title":"Identification of patients with Fabry disease using routine pathology results: PATHFINDER (eGFR) study","volume":"75","author":"Reynolds","year":"2021","journal-title":"Int J Clin Pract"},{"key":"2025101712554073000_60.4.391.11","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.nephro.2021.03.002","article-title":"Screening for Fabry disease in male patients with end-stage renal disease in Western France","volume":"17","author":"Vigneau","year":"2021","journal-title":"Nephrol Ther"},{"key":"2025101712554073000_60.4.391.12","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.1016\/j.jstrokecerebrovasdis.2018.08.025","article-title":"Screening for Fabry disease in Japanese patients with young-onset stroke by measuring \u03b1-galactosidase A and globotriaosylsphingosine","volume":"27","author":"Kinoshita","year":"2018","journal-title":"Journal of Stroke and Cerebrovascular Diseases"},{"key":"2025101712554073000_60.4.391.13","first-page":"44","article-title":"Acute cerebrovascular disease in the young: the stroke in young Fabry patients study","author":"Rolfs","year":"2013","journal-title":"Stroke"},{"key":"2025101712554073000_60.4.391.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0579-z"},{"key":"2025101712554073000_60.4.391.15","doi-asserted-by":"crossref","unstructured":"Karczewski KJ , Francioli LC , Tiao G , Cummings BB , Alfoldi J , Wang Q , Collins RL , Laricchia KM , Ganna A , Birnbaum DP , Gauthier LD , Brand H , Solomonson M , Watts NA , Rhodes D , Singer-Berk M , England EM , Seaby EG , Kosmicki JA , Walters RK , Tashman K , Farjoun Y , Banks E , Poterba T , Wang A , Seed C , Whiffin N , Chong JX , Samocha KE , Pierce-Hoffman E , Zappala Z , O'Donnell-Luria AH , Minikel EV , Weisburd B , Lek M , Ware JS , Vittal C , Armean IM , Bergelson L , Cibulskis K , Connolly KM , Covarrubias M , Donnelly S , Ferriera S , Gabriel S , Gentry J , Gupta N , Jeandet T , Kaplan D , Llanwarne C , Munshi R , Novod S , Petrillo N , Roazen D , Ruano-Rubio V , Saltzman A , Schleicher M , Soto J , Tibbetts K , Tolonen C , Wade G , Talkowski ME . Genome aggregation database C, Neale BM, Daly MJ, MacArthur dG. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 2020:581\u201343.","DOI":"10.1038\/s41586-020-2308-7"},{"key":"2025101712554073000_60.4.391.16","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2025101712554073000_60.4.391.17","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-0337"},{"key":"2025101712554073000_60.4.391.18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0193550"},{"key":"2025101712554073000_60.4.391.19","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19123726","article-title":"Mutations in the GLA gene and LysoGb3: is it really Anderson-Fabry disease?","volume":"19","author":"Duro","year":"2018","journal-title":"Int J Mol Sci"},{"key":"2025101712554073000_60.4.391.20","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/cge.13694","article-title":"Diagnostic strategy for females suspected of Fabry disease","volume":"97","author":"Balendran","year":"2020","journal-title":"Clin Genet"},{"key":"2025101712554073000_60.4.391.21","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/mgg3.389","article-title":"Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease: A multicenter Fabry Registry study","volume":"6","author":"Germain","year":"2018","journal-title":"Mol Genet Genomic Med"},{"key":"2025101712554073000_60.4.391.22","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-007-0521-2"},{"key":"2025101712554073000_60.4.391.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.12.015"},{"key":"2025101712554073000_60.4.391.24","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwx246"},{"key":"2025101712554073000_60.4.391.25","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/humu.21530","article-title":"A pharmacogenetic approach to identify mutant forms of \u03b1-galactosidase a that respond to a pharmacological chaperone for Fabry disease","volume":"32","author":"Wu","year":"2011","journal-title":"Hum Mutat"},{"key":"2025101712554073000_60.4.391.26","article-title":"Two related Chinese Fabry disease patients with a p.N215S pathological variant who presented with nephropathy","volume":"24","author":"Sheng","year":"2020","journal-title":"Mol Genet Metab Rep"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg-2022-108523","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T19:55:52Z","timestamp":1760730952000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg-2022-108523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,17]]},"references-count":26,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,3,20]]},"published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1136\/jmg-2022-108523"],"URL":"https:\/\/doi.org\/10.1136\/jmg-2022-108523","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,17]]}}}