{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:40:41Z","timestamp":1792129241150,"version":"4.4.0"},"reference-count":42,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010733","name":"Danish Childhood Cancer Foundation","doi-asserted-by":"crossref","award":["2019-5934"],"award-info":[{"award-number":["2019-5934"]}],"id":[{"id":"10.13039\/100010733","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008363","name":"Danish Cancer Society","doi-asserted-by":"crossref","award":["R-257-A14720"],"award-info":[{"award-number":["R-257-A14720"]}],"id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2023,3,10]]},"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Studies suggest that Wilms tumours (WT) are caused by underlying genetic (5%\u201310%) and epigenetic (2%\u201329%) mechanisms, yet studies covering both aspects are sparse.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed prospective whole-genome sequencing of germline DNA in Danish children diagnosed with WT from 2016 to 2021, and linked genotypes to deep phenotypes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 24 patients (58% female), 3 (13%, all female) harboured pathogenic germline variants in WT risk genes (<jats:italic>FBXW7, WT1<\/jats:italic> and <jats:italic>REST<\/jats:italic>). Only one patient had a family history of WT (3 cases), segregating with the <jats:italic>REST<\/jats:italic> variant. Epigenetic testing revealed one (4%) additional patient (female) with uniparental disomy of chromosome 11 and Beckwith-Wiedemann syndrome (BWS). We observed a tendency of higher methylation of the BWS-related imprinting centre 1 in patients with WT than in healthy controls. Three patients (13%, all female) with bilateral tumours and\/or features of BWS had higher birth weights (4780 g vs 3575 g; p=0.002). We observed more patients with macrosomia (&gt;4250 g, n=5, all female) than expected (OR 9.98 (95% CI 2.56 to 34.66)). Genes involved in early kidney development were enriched in our constrained gene analysis, including both known (<jats:italic>WT1<\/jats:italic>, <jats:italic>FBXW7<\/jats:italic>) and candidate (<jats:italic>CTNND1, FRMD4A<\/jats:italic>) WT predisposition genes. WT predisposing variants, BWS and\/or macrosomia (n=8, all female) were more common in female patients than male patients (p=0.01).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We find that most females (57%) and 33% of all patients with WT had either a genetic or another indicator of WT predisposition. This emphasises the need for scrutiny when diagnosing patients with WT, as early detection of underlying predisposition may impact treatment, follow-up and genetic counselling.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2022-108982","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T14:10:34Z","timestamp":1680703834000},"page":"842-849","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Germline (epi)genetics reveals high predisposition in females: a 5-year, nationwide, prospective Wilms tumour cohort"],"prefix":"10.1136","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5862-3292","authenticated-orcid":false,"given":"Ulrik Kristoffer","family":"Stoltze","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark"},{"name":"Department of Pediatrics, Rigshospitalet, Copenhagen, 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