{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T20:28:34Z","timestamp":1776198514715,"version":"3.50.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Dyskeratosis congenita (DKC), also known as Zinsser\u2013Cole\u2013Engman syndrome, is a telomeropathy typically presenting as a triad of leukoplakia, nail dystrophy, and reticular hyperpigmentation. Reported genetic mutations linked to DKC include <jats:italic>DKC1<\/jats:italic>, <jats:italic>TINF2<\/jats:italic>, <jats:italic>TERC<\/jats:italic>, <jats:italic>TERT<\/jats:italic>, <jats:italic>C16orf57<\/jats:italic>, <jats:italic>NOLA2<\/jats:italic>, <jats:italic>NOLA3<\/jats:italic>, <jats:italic>WRAP53\/TCAB1<\/jats:italic>, and <jats:italic>RTEL1<\/jats:italic>. Homozygous, compound heterozygous, and heterozygous mutations in <jats:italic>RTEL1<\/jats:italic> (<jats:italic>RTEL1<\/jats:italic>, regulator of telomere elongation helicase 1) gene on chromosome 20q13 are known to cause autosomal dominant as well as recessive DKC. Pathogenic variants of <jats:italic>RTEL1<\/jats:italic> gene in <jats:italic>DKC<\/jats:italic> patients include c.2288G&amp;gt;T (p. Gly763Val), c.3791G&amp;gt;A (p. Arg1264His), and <jats:italic>RTEL<\/jats:italic> p. Arg981Trp. We report a novel homozygous variant of <jats:italic>RTEL1<\/jats:italic>, transcript ID: ENST00000360203.11, exon 24, c.2060C&amp;gt;T (p.Ala687Val), in a patient of DKC presenting with leukoplakia, dystrophic nails, reticulate pigmentation, and positive family history of a similar phenotype. The novel variant, reported as a variant of uncertain significance, may therefore be considered diagnostic for DKC in a Pakistani population.<\/jats:p>","DOI":"10.3389\/fonc.2023.1098876","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T05:53:47Z","timestamp":1677736427000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case report: A novel mutation in RTEL1 gene in dyskeratosis congenita"],"prefix":"10.3389","volume":"13","author":[{"given":"Haider","family":"Nisar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Memoona","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qamar Un Nisa","family":"Chaudhry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raheel","family":"Iftikhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tariq","family":"Ghafoor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13030496","article-title":"Multisystemic manifestations in rare diseases: the experience of dyskeratosis congenita","volume":"13","author":"Callea","year":"2022","journal-title":"Genes"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e226736","DOI":"10.1136\/bcr-2018-226736","article-title":"Dyskeratosis congenita: presentation of cutaneous triad in a sporadic case","volume":"11","author":"Sharma","year":"2018","journal-title":"BMJ Case Rep CP"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.949435","article-title":"Fanconi anemia and dyskeratosis congenita\/telomere biology disorders: Two inherited bone marrow failure syndromes with genomic instability","volume":"2022","author":"Fiesco-Roa","year":"","journal-title":"Front Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2019.1662720","article-title":"An update on the biology and management of dyskeratosis congenita and related telomere biology disorders","volume":"12","author":"Niewisch","year":"2019","journal-title":"Expert Rev hematol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s12890-021-01645-w","article-title":"Pulmonary fibrosis in dyskeratosis congenita:a case report with PRISMA-compliant systematic review","volume":"21","author":"Wang","year":"2021","journal-title":"BMC Pulm Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2018.10.009","article-title":"A rigorous interlaboratory examination of the need to confirm next-generation sequencing-detected variants with an orthogonal method in clinical genetic testing","volume":"21","author":"Lincoln","year":"2019","journal-title":"J Mol Diagn"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.10.e47","article-title":"Telomere measurement by quantitative PCR","volume":"30","author":"Cawthon","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2011.1.480","article-title":"Dyskeratosis congenita","volume":"2011","author":"Dokal","year":"2011","journal-title":"Hematol Am Soc Hematol Educ Program"},{"key":"B9","article-title":"Diagnosis, genetics, and management of inherited bone marrow failure syndromes","volume":"2007","author":"Alter","year":"2007","journal-title":"ASH Education Program Book"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0903373","article-title":"Telomere diseases","volume":"361","author":"Calado","year":"2009","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.055269","article-title":"Savage SA.Telomere length is associated with disease severity and declines with age in dyskeratosis congenita","volume":"97","author":"Alter","year":"2012","journal-title":"Haematologica"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.834268","article-title":"Case report: A missense mutation in dyskeratosis congenita 1 leads to a benign form of dyskeratosis congenita syndrome with the mucocutaneous triad","volume":"10","author":"Wang","year":"2022","journal-title":"Front Pediatr"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/ddg.14268","article-title":"Dyskeratosis congenita: a literature review","volume":"18","author":"AlSabbagh","year":"2020","journal-title":"J Dtsch Dermatol Ges"},{"key":"B14","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/s12881-018-0584-y","article-title":"Dyskeratosis congenita with a novel genetic variant in the DKC1 gene: a case report","volume":"19","author":"Ratnasamy","year":"2018","journal-title":"BMC Med Genet"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1045","article-title":"RTEL1: an essential helicase for telomere maintenance and the regulation of homologous recombination","volume":"39","author":"Uringa","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E12-03-0179","article-title":"RTEL1 contributes to DNA replication and repair and telomere maintenance","volume":"23","author":"Uringa","year":"2012","journal-title":"Mol Biol Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.cell.2012.03.030","article-title":"RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity","volume":"149","author":"Vannier","year":"2012","journal-title":"Cell"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-022-00407-x","article-title":"Expanding ACMG variant classification guidelines into a general framework","volume":"16","author":"Masson","year":"2022","journal-title":"Hum Genomics"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00449","article-title":"Clinical and molecular heterogeneity of RTEL1 deficiency","volume":"8","author":"Speckmann","year":"2017","journal-title":"Front Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/10428199409051671","article-title":"Dyskeratosis congenita is a chromosomal instability disorder","volume":"15","author":"Dokal","year":"1994","journal-title":"Leuk Lymphoma"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1265-8","article-title":"Germline mutations of regulator of telomere elongation helicase 1, RTEL1, in dyskeratosis congenita","volume":"132","author":"Ballew","year":"2013","journal-title":"Hum Genet"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00308-2016","article-title":"Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive","volume":"48","author":"Newton","year":"2016","journal-title":"Eur Respir J"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00040115","article-title":"Heterozygous RTEL1 mutations are associated with familial pulmonary fibrosis","volume":"46","author":"Kannengiesser","year":"2015","journal-title":"Eur Respir J"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3278","article-title":"Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening","volume":"47","author":"Stuart","year":"2015","journal-title":"Nat Genet"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)08256-1","article-title":"Accelerated telomere shortening in young recipients of allogeneic bone-marrow transplants","volume":"351","author":"Wynn","year":"1998","journal-title":"Lancet"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2013.05.021","article-title":"Outcomes of allogeneic hematopoietic cell transplantation in patients with dyskeratosis congenita","volume":"19","author":"Gadalla","year":"2013","journal-title":"Biol Blood Marrow Transplant"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1098876\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T05:53:51Z","timestamp":1677736431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1098876\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,2]]},"references-count":27,"alternative-id":["10.3389\/fonc.2023.1098876"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2023.1098876","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,2]]},"article-number":"1098876"}}