{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:02:15Z","timestamp":1791302535471,"version":"4.1.0"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2013,8,29]],"date-time":"2013-08-29T00:00:00Z","timestamp":1377734400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"DOI":"10.1371\/journal.pgen.1003695","type":"journal-article","created":{"date-parts":[[2013,8,29]],"date-time":"2013-08-29T22:04:01Z","timestamp":1377813841000},"page":"e1003695","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":141,"title":["A Recessive Founder Mutation in Regulator of Telomere Elongation Helicase 1, RTEL1, Underlies Severe Immunodeficiency and Features of Hoyeraal Hreidarsson Syndrome"],"prefix":"10.1371","volume":"9","author":[{"given":"Bari J.","family":"Ballew","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijai","family":"Joseph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurav","family":"De","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Sarek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Baptiste","family":"Vannier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Stracker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasmintan A.","family":"Schrader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trudy N.","family":"Small","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"O'Reilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Manschreck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan M.","family":"Harlan Fleischut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Stratton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith","family":"Yeager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelam","family":"Giri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanche P.","family":"Alter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Boland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Burdett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Offit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Boulton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon A.","family":"Savage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H. J.","family":"Petrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,8,29]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1097\/GIM.0b013e3181f415b5","article-title":"The genetics and clinical manifestations of telomere biology disorders","volume":"12","author":"SA Savage","year":"2010","journal-title":"Genet Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1365-2141.2010.08212.x","article-title":"Malignancies and survival patterns in the National Cancer Institute inherited bone marrow failure syndromes cohort study","volume":"150","author":"BP Alter","year":"2010","journal-title":"Br J Haematol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3324\/haematol.2011.055269","article-title":"Telomere length is associated with disease severity and declines with age in dyskeratosis congenita","volume":"97","author":"BP Alter","year":"2012","journal-title":"Haematologica"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.mrfmmm.2011.06.008","article-title":"Dyskeratosis congenita as a disorder of telomere maintenance","volume":"730","author":"ND Nelson","year":"2012","journal-title":"Mutat Res"},{"issue":"3","key":"ref5","doi-asserted-by":"crossref","first-page":"334","DOI":"10.3324\/haematol.2012.071068","article-title":"Mutations in the telomere capping complex in bone marrow failure and related syndromes","volume":"98","author":"A Walne","year":"2012","journal-title":"Haematologica"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"473","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":"BJ Ballew","year":"2013","journal-title":"Hum Genet"},{"issue":"3","key":"ref7","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.ajhg.2013.02.001","article-title":"Constitutional Mutations in RTEL1 Cause Severe Dyskeratosis Congenita","volume":"92","author":"AJ Walne","year":"2013","journal-title":"Am J Hum Genet"},{"issue":"16","key":"ref8","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1093\/hmg\/ddt178","article-title":"Human RTEL1 deficiency causes Hoyeraal-Hreidarsson syndrome with short telomeres and genome instability","volume":"22","author":"T Le Guen","year":"2013","journal-title":"Hum Mol Genet"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/j.1399-3038.2010.01136.x","article-title":"Dyskeratosis congenita: a combined immunodeficiency with broad clinical spectrum\u2013a single-center pediatric experience","volume":"22","author":"S Jyonouchi","year":"2011","journal-title":"Pediatr Allergy Immunol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.jaci.2003.07.003","article-title":"Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study","volume":"112","author":"WT Shearer","year":"2003","journal-title":"J Allergy Clin Immunol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/pbc.24193","article-title":"CTC1 Mutations in a patient with dyskeratosis congenita","volume":"59","author":"RB Keller","year":"2012","journal-title":"Pediatr Blood Cancer"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature09534","article-title":"A map of human genome variation from population-scale sequencing","volume":"467","author":"GP Consortium","year":"2010","journal-title":"Nature"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e1002772","DOI":"10.1371\/journal.pgen.1002772","article-title":"Loss of ATRX, genome instability, and an altered DNA damage response are hallmarks of the alternative lengthening of telomeres pathway","volume":"8","author":"CA Lovejoy","year":"2012","journal-title":"PLoS genetics"},{"key":"ref14","doi-asserted-by":"crossref","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":"JB Vannier","year":"2012","journal-title":"Cell"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.molcel.2007.05.025","article-title":"Ku suppresses formation of telomeric circles and alternative telomere lengthening in Arabidopsis","volume":"27","author":"B Zellinger","year":"2007","journal-title":"Molecular Cell"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.cell.2008.08.016","article-title":"RTEL1 maintains genomic stability by suppressing homologous recombination","volume":"135","author":"LJ Barber","year":"2008","journal-title":"Cell"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.cell.2008.10.003","article-title":"Ensuring an exit strategy: RTEL1 restricts rogue recombination","volume":"135","author":"AM Villeneuve","year":"2008","journal-title":"Cell"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"9948","DOI":"10.1128\/MCB.24.22.9948-9957.2004","article-title":"Telomeric DNA in ALT cells is characterized by free telomeric circles and heterogeneous t-loops","volume":"24","author":"AJ Cesare","year":"2004","journal-title":"Mol Cell Biol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.cell.2004.05.026","article-title":"Regulation of murine telomere length by Rtel: an essential gene encoding a helicase-like protein","volume":"117","author":"H Ding","year":"2004","journal-title":"Cell"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-1-4419-6448-9_16","article-title":"Ligase IV syndrome","volume":"685","author":"DA Chistiakov","year":"2010","journal-title":"Adv Exp Med Biol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.blre.2010.03.002","article-title":"Pathophysiology and management of inherited bone marrow failure syndromes","volume":"24","author":"A Shimamura","year":"2010","journal-title":"Blood Rev"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1146\/annurev.biochem.78.101807.093809","article-title":"RING domain E3 ubiquitin ligases","volume":"78","author":"RJ Deshaies","year":"2009","journal-title":"Annu Rev Biochem"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1038\/ng.408","article-title":"Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility","volume":"41","author":"M Wrensch","year":"2009","journal-title":"Nat Genet"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/ng.407","article-title":"Genome-wide association study identifies five susceptibility loci for glioma","volume":"41","author":"S Shete","year":"2009","journal-title":"Nat Genet"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s11060-010-0506-0","article-title":"Cancer susceptibility variants and the risk of adult glioma in a US case-control study","volume":"104","author":"KM Egan","year":"2011","journal-title":"J Neurooncol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1038\/nprot.2006.263","article-title":"Flow cytometry and FISH to measure the average length of telomeres (flow FISH)","volume":"1","author":"GM Baerlocher","year":"2006","journal-title":"Nat Protoc"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"MA DePristo","year":"2011","journal-title":"Nat Genet"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"3216","DOI":"10.1093\/bioinformatics\/btr540","article-title":"Kaviar: an accessible system for testing SNV novelty","volume":"27","author":"G Glusman","year":"2011","journal-title":"Bioinformatics"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/nar\/29.1.308","article-title":"dbSNP: the NCBI database of genetic variation","volume":"29","author":"ST Sherry","year":"2001","journal-title":"Nucleic Acids Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/nbt.1583","article-title":"Microdroplet-based PCR enrichment for large-scale targeted sequencing","volume":"27","author":"R Tewhey","year":"2009","journal-title":"Nat Biotechnol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"IA Adzhubei","year":"2010","journal-title":"Nat Methods"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/nprot.2009.86","article-title":"Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm","volume":"4","author":"P Kumar","year":"2009","journal-title":"Nat Protoc"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.ajhg.2011.03.004","article-title":"Improving the assessment of the outcome of nonsynonymous SNVs with a consensus deleteriousness score, Condel","volume":"88","author":"A Gonzalez-Perez","year":"2011","journal-title":"Am J Hum Genet"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1006\/jmbi.2000.4042","article-title":"T-Coffee: A novel method for fast and accurate multiple sequence alignment","volume":"302","author":"C Notredame","year":"2000","journal-title":"J Mol Biol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"5540","DOI":"10.1128\/MCB.00479-09","article-title":"The mre11 complex and the response to dysfunctional telomeres","volume":"29","author":"CL Attwooll","year":"2009","journal-title":"Mol Cell Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1093\/emboj\/20.3.579","article-title":"t-loops at trypanosome telomeres","volume":"20","author":"JL Munoz-Jordan","year":"2001","journal-title":"EMBO J"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.molcel.2007.05.025","article-title":"Ku suppresses formation of telomeric circles and alternative telomere lengthening in Arabidopsis","volume":"27","author":"B Zellinger","year":"2007","journal-title":"Mol Cell"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1128\/MCB.01354-08","article-title":"Artemis and nonhomologous end joining-independent influence of DNA-dependent protein kinase catalytic subunit on chromosome stability","volume":"29","author":"TH Stracker","year":"2009","journal-title":"Molecular and Cellular Biology"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/ncb1275","article-title":"DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion","volume":"7","author":"GB Celli","year":"2005","journal-title":"Nat Cell Biol"}],"container-title":["PLoS Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pgen.1003695","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T12:49:39Z","timestamp":1715950179000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1003695"}},"subtitle":[],"editor":[{"given":"Hamish S.","family":"Scott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,8,29]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2013,8,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1003695","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,29]]}}}