{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:13:51Z","timestamp":1789517631623,"version":"build-2803163510"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"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":[[2026,3]]},"abstract":"ABSTRACT<\/jats:title>\n \n Dilated Cardiomyopathy (DCM) is a genetically heterogeneous condition of left ventricular dilation and systolic dysfunction, leading to heart failure. It is mostly inherited in a dominant pattern. Recessive inheritance has been rarely encountered. This study aims to outline the clinical and genetic characteristics associated with recessively inherited\n NRAP<\/jats:italic>\n truncating variants in our highly consanguineous population. Twenty\u2010three cases from 12 unrelated consanguineous families were recruited. Cardiological evaluation and genetic testing with exome sequencing (ES) were conducted in all cases, followed by segregation analysis of first\u2010degree relatives. Genetic analysis with ES identified five unique homozygous truncating variants in\n NRAP<\/jats:italic>\n in the affected cases. The segregation analysis detected a total of 23 homozygous and 21 heterozygous individuals. Out of the total homozygous cases, three were asymptomatic, while 20 exhibited symptoms with remarkable inter\u2010 and intrafamilial variability of the age of onset (range: 9\u2009months to 47\u2009years, median 10\u2009years), seven of whom died (range: 9\u2009months to 28\u2009years, median 7\u2009years). None of the heterozygous individuals showed symptoms. Of note, three homozygous cases underwent heart transplantation. Our findings show that truncating variants in\n NRAP<\/jats:italic>\n are associated with reduced penetrance and clinical variability, suggesting a complex mechanism beyond simple Mendelian inheritance.\n <\/jats:p>","DOI":"10.1111\/cge.70078","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T23:29:55Z","timestamp":1759361395000},"page":"598-603","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reduced Penetrance and Variable Expression of Dilated Cardiomyopathy Associated With Homozygous Truncating Variants in\n \n NRAP<\/i>\n <\/scp>\n Gene"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0801-6295","authenticated-orcid":false,"given":"Aisha","family":"Alqahtani","sequence":"first","affiliation":[{"name":"Cardiovascular Genetics Program, Department of Translational Genomics, Genomic Medicine Center of Excellence (GMCoE) King Faisal Specialist Hospital & Research Center (KFSH&RC) Riyadh Saudi Arabia"},{"name":"College of Medicine, Alfaisal University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Tulbah","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Program, Department of Translational Genomics, Genomic Medicine Center of Excellence (GMCoE) King Faisal Specialist Hospital & Research Center (KFSH&RC) Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadiah","family":"Alruwaili","sequence":"additional","affiliation":[{"name":"Heart Centre of Excellence KFSH&RC Riyadh Saudi\u00a0Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saud","family":"Takroni","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Program, Department of Translational Genomics, Genomic Medicine Center of Excellence (GMCoE) King Faisal Specialist Hospital & Research Center (KFSH&RC) Riyadh Saudi Arabia"},{"name":"Medical Genomics Department GMCoE, KFSH&RC Riyadh Saudi\u00a0Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarab","family":"Alkorashy","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Program, Department of Translational Genomics, Genomic Medicine Center of Excellence (GMCoE) King Faisal Specialist Hospital & Research Center (KFSH&RC) Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed","family":"Manea","sequence":"additional","affiliation":[{"name":"Heart Centre of Excellence KFSH&RC Riyadh Saudi\u00a0Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimpna C.","family":"Albert Brotons","sequence":"additional","affiliation":[{"name":"Heart Centre of Excellence KFSH&RC Riyadh Saudi\u00a0Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Alwadai","sequence":"additional","affiliation":[{"name":"Heart Failure & Transplant Program, Prince Sultan Cardiac Center Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jehad","family":"Alburaiki","sequence":"additional","affiliation":[{"name":"Heart Centre of Excellence KFSH&RC Riyadh Saudi\u00a0Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4158-341X","authenticated-orcid":false,"given":"Fowzan","family":"Alkuraya","sequence":"additional","affiliation":[{"name":"Lifera Omics Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadiah","family":"Al\u2010Hashmi","sequence":"additional","affiliation":[{"name":"Department of Child Health, National Genetic Center Royal Hospital Muscat Sultanate of Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samah","family":"Zarroug","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7173-2044","authenticated-orcid":false,"given":"Zuhair N.","family":"Al\u2010Hassnan","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Program, Department of Translational Genomics, Genomic Medicine Center of Excellence (GMCoE) King Faisal Specialist Hospital & Research Center (KFSH&RC) Riyadh Saudi Arabia"},{"name":"College of Medicine, Alfaisal University Riyadh Saudi Arabia"},{"name":"Medical Genomics Department GMCoE, KFSH&RC Riyadh Saudi\u00a0Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu301"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.cj\u201014\u20100893"},{"key":"e_1_2_9_4_1","volume-title":"GeneReviews","author":"Hershberger R. 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