{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T23:02:20Z","timestamp":1768345340661,"version":"3.49.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Interstitial lung disease (ILD) is a condition affecting the lung parenchyma by inflammation and fibrosis and can be caused by various exposures, connective tissue diseases (CTD), and genetic disorders. In this report, a family with five patients having progressive respiratory failure that begins with coughing in adolescence, followed by dyspnea and recurrent spontaneous pneumothorax, and death in early adulthood is presented. The patients were diagnosed to have ILD through clinical and radiological evaluations. Molecular genetic analyses of the family provided two homozygous rare variants in the <jats:italic>WRN<\/jats:italic> and <jats:italic>SFXN5<\/jats:italic> genes, co\u2010segregating with the phenotype. The network analyses pointed out that the variant in the <jats:italic>WRN<\/jats:italic>, rather than that in the <jats:italic>SFXN5<\/jats:italic> gene, could be the main factor in the existence of the ILD phenotype, putatively through the altered DNA repair and telomere maintenance pathways. In silico analyses suggested that the variant could affect the exonuclease activity or the stability of the WRN protein. Moreover, the adolescent\u2010onset pulmonary phenotype described in the case has not been reported in Werner Syndrome, the only disease known to be associated with biallelic <jats:italic>WRN<\/jats:italic> pathogenic variants. Thus, the present phenotype could be either a very atypical presentation of Werner syndrome or a new clinical entity associated with the <jats:italic>WRN<\/jats:italic> gene.<\/jats:p>","DOI":"10.1002\/ajmg.a.62986","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T14:19:21Z","timestamp":1665411561000},"page":"220-227","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A homozygous missense variant in the <scp><i>WRN<\/i><\/scp> gene segregating in a family with progressive pulmonary failure with recurrent spontaneous pneumothorax and interstitial lung disease"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3886-3808","authenticated-orcid":false,"given":"Abdullah","family":"Sezer","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Dr. Sami Ulus Maternity and Children's Training and Research Hospital  Ankara Turkey"},{"name":"Department of Medical Genetics, Faculty of Medicine Gazi University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gulsum","family":"Kayhan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Gazi University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tugba Ramasli","family":"Gursoy","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, Faculty of Medicine Gazi University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tugba Sismanlar","family":"Eyuboglu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, Faculty of Medicine Gazi University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferda E.","family":"Percin","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Gazi University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13526"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1389"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008543"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2014.02.006"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060713-035428"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky471"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.035600"},{"key":"e_1_2_9_9_1","volume-title":"GeneReviews(\u00ae)","author":"Flanagan M.","year":"1993"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx352"},{"key":"e_1_2_9_11_1","volume-title":"GeneReviews(\u00ae)","author":"Garcia C. 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