{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:56:15Z","timestamp":1773053775271,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Whilst biallelic variants in\n                    <jats:italic>RTEL1<\/jats:italic>\n                    are an established cause of telomere biology disorder (TBD), the significance of heterozygous variants has been more challenging to establish. In this nationwide analysis, we describe 18 individuals with heterozygous pathogenic\n                    <jats:italic>RTEL1<\/jats:italic>\n                    variants from seven families. All were identified during routine clinical genetic investigation for a variety of indications. Each family carried a different variant in\n                    <jats:italic>RTEL1<\/jats:italic>\n                    . Eight individuals had been diagnosed with a TBD\u2010related disease (five with a hematological disorder, four with pulmonary fibrosis, overlap of one). No cases of clinically significant liver fibrosis had been detected. Cutaneous features of dyskeratosis congenita (abnormal skin pigmentation, oral leukoplakia, nail dysplasia and\/or prematurely gray hair) were observed in four individuals. Telomere length (lymphocyte) was measured in nine individuals from six families and was below the 1st percentile in eight individuals. These cases illustrate the wide spectrum of disease and reduced penetrance associated with pathogenic\n                    <jats:italic>RTEL1<\/jats:italic>\n                    variants, providing a real\u2010world perspective on previous findings from research cohorts. We discuss the challenges surrounding incidental findings, clinical surveillance, and reproductive counseling in this context.\n                  <\/jats:p>","DOI":"10.1002\/ajmga.70015","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T07:49:49Z","timestamp":1764748189000},"page":"959-965","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Series: Clinical Significance of Heterozygous Pathogenic\n                    <scp>\n                      <i>RTEL1<\/i>\n                    <\/scp>\n                    Variants Identified via Routine Clinical Genetic Diagnostics"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3756-6094","authenticated-orcid":false,"given":"Eileen","family":"Wedge","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Department of Hematology Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Biotech Research and Innovation Center (BRIC) University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas \u00d8rslev","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Line","family":"Borgwardt","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack Bernard","family":"Cowland","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1535-9601","authenticated-orcid":false,"given":"Kirsten","family":"Gr\u00f8nb\u00e6k","sequence":"additional","affiliation":[{"name":"Department of Hematology Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Biotech Research and Innovation Center (BRIC) University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Issa Ismail","family":"Issa","sequence":"additional","affiliation":[{"name":"Department of Hematology Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Biotech Research and Innovation Center (BRIC) University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lone Smidstrup","family":"Friis","sequence":"additional","affiliation":[{"name":"Department of Hematology Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mette Klarskov","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie Skov","family":"Hvidbjerg","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Aalborg University Hospital  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne Marie","family":"Jelsig","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital  Copenhagen 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