{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:47:15Z","timestamp":1791229635222,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"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":["Clinical Genetics"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Dyskeratosis congenita (DC) is a rare genetic disorder caused by impaired telomere maintenance, leading to diverse clinical manifestations, including bone marrow failure, mucocutaneous abnormalities, and multi\u2010organ dysfunction. Here, we report a 14\u2010year\u2010old male patient presenting with microcephaly, developmental delay, synostoses, cerebellar hypoplasia with ataxia, and an immunodeficiency condition, but lacking classical DC features such as nail dystrophy and skin hyperpigmentation. WGS revealed two variants in the\n                    <jats:italic>PARN<\/jats:italic>\n                    gene: a known pathogenic missense variant (c.1045C\u2009&gt;\u2009T, p.Arg349Trp) and a novel intronic variant (c.178\u201028T\u2009&gt;\u2009C). Functional RNA analysis demonstrated that the intronic variant disrupts the branch point sequence, leading to exon 4 skipping and nonsense\u2010mediated decay (NMD) of a significant proportion of transcripts. This study confirms the pathogenicity of the intronic variant and underscores the importance of functional validation in interpreting noncoding variants, particularly in genetically heterogeneous disorders like DC. Our findings expand the molecular and phenotypic spectrum of\n                    <jats:italic>PARN<\/jats:italic>\n                    \u2010related DC and highlight the utility of WGS reanalysis and RNA studies in resolving diagnostically challenging cases.\n                  <\/jats:p>","DOI":"10.1111\/cge.70037","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T03:26:17Z","timestamp":1756265177000},"page":"346-351","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>RNA<\/scp>\n                    Analysis Uncovers Pathogenic\n                    <scp>PARN<\/scp>\n                    Variant in Dyskeratosis Congenita"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7001-4099","authenticated-orcid":false,"given":"Daria","family":"Akimova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Semenova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Cherevatova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7293-3438","authenticated-orcid":false,"given":"Mikhail","family":"Skoblov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ddg.14268"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.5001\/omj.2015.44"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2015.10.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3278"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2022.2108784"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2622"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2019.1662720"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2022000394"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ced\/llae211"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI78963"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103292"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13690-023-01112-4"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-020-05758-6"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MS9.0000000000002661"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-022-01073-3"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21062"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-022-01177-9"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70037","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70037","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70037","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:42:01Z","timestamp":1776645721000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":17,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/cge.70037"],"URL":"https:\/\/doi.org\/10.1111\/cge.70037","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.70037\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70037\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70037\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70037\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70037\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70037\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,26]]},"assertion":[{"value":"2025-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}