{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:02:59Z","timestamp":1780473779762,"version":"3.54.1"},"reference-count":16,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"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":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pediatric dilated cardiomyopathy (DCM) carries high morbidity and mortality, with up to half of cases genetically unexplained. The mTORC1 nutrient sensing pathway is a critical regulator of cardiomyocyte homeostasis, yet no Mendelian DCM genes have been linked to its upstream regulator, GATOR2.\n                    <jats:italic>WDR59<\/jats:italic>\n                    encodes a core WD\u2010repeat subunit of GATOR2, but its cardiac role is unknown. We recruited six affected individuals from four unrelated families presenting with early\u2010onset, severe autosomal recessive syndromic DCM. Affected children developed left ventricular dilation, variably accompanied by cataracts, dysmorphic facial features, and growth and developmental delay. Saudi patients mapped to a single locus and shared therein a homozygous founder\n                    <jats:italic>WDR59<\/jats:italic>\n                    variant: c.2887G&gt;A (p.Gly963Arg). The French patient was compound heterozygous for two variants (NM_030581.4:c.966+3A&gt;G and NM_030581.4:c.886+1219T&gt;G) and their deleterious splicing effect was confirmed by RNA\u2010seq. We propose\n                    <jats:italic>WDR59<\/jats:italic>\n                    as a novel autosomal recessive DCM gene and implicate dysregulated GATOR2\u2013mTORC1 signaling as the underlying mechanism. Future validation is needed to confirm this link and investigate whether restoring mTORC1\u2013autophagy balance can ameliorate\n                    <jats:italic>WDR59<\/jats:italic>\n                    \u2010related cardiac dysfunction.\n                  <\/jats:p>","DOI":"10.1111\/cge.70151","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T06:50:48Z","timestamp":1771570248000},"page":"84-89","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>WDR59<\/i>\n                    Is Mutated in Individuals With Autosomal Recessive Syndromic Dilated Cardiomyopathy"],"prefix":"10.1111","volume":"110","author":[{"given":"Lama","family":"Alabdi","sequence":"first","affiliation":[{"name":"Department of Translational Genomics, Genomic Medicine Center of Excellence King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Cogne","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale Nantes Universit\u00e9, CHU de Nantes  Nantes France"},{"name":"CHU de Nantes, CNRS, INSERM, L'institut du Thorax, F\u201044000 Nantes Universit\u00e9  Nantes France"},{"name":"Laboratoire de Biologie M\u00e9dicale Multi\u2010Sites SeqOIA (laboratoire\u2010seqoia.fr)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7854-7984","authenticated-orcid":false,"given":"Ali S.","family":"Almasood","sequence":"additional","affiliation":[{"name":"Adult Cardiology Department King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Alsehly","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology Department King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Helaby","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, Genomic Medicine Center of Excellence King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2999-2229","authenticated-orcid":false,"given":"Sateesh","family":"Maddirevula","sequence":"additional","affiliation":[{"name":"Precision Medicine Laboratory, Genomic Medicine Center of Excellence King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"},{"name":"College of Medicine Alfaisal University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Besnard","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale Nantes Universit\u00e9, CHU de Nantes  Nantes France"},{"name":"CHU de Nantes, CNRS, INSERM, L'institut du Thorax, F\u201044000 Nantes Universit\u00e9  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Do Souto","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale Nantes Universit\u00e9, CHU de Nantes  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Isidor","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale Nantes Universit\u00e9, CHU de Nantes  Nantes France"},{"name":"CHU de Nantes, CNRS, INSERM, L'institut du Thorax, F\u201044000 Nantes Universit\u00e9  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fowzan S.","family":"Alkuraya","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, Genomic Medicine Center of Excellence King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"},{"name":"College of Medicine Alfaisal University  Riyadh Saudi Arabia"},{"name":"Lifera Omics  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.296.15.1867"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2013.105"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62862"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-025-01635-0"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyae031"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22844"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.04.011"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-025-01529-2"},{"issue":"3","key":"e_1_2_10_10_1","article-title":"Arab Founder Variants: Contributions to Clinical Genomics and Precision Medicine","volume":"6","author":"AlAbdi 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