{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:51:16Z","timestamp":1791471076004,"version":"4.3.4"},"reference-count":20,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004919","name":"King Abdulaziz City for Science and Technology","doi-asserted-by":"publisher","award":["08\u2010MED489\u201020"],"award-info":[{"award-number":["08\u2010MED489\u201020"]}],"id":[{"id":"10.13039\/501100004919","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Congenital heart disease (CHD) is the most common type of birth defect with tremendous genetic heterogeneity. The aim of our study was to unravel the molecular pathology and the magnitude of recessive genotypes (RGs) in a cohort of CHD from our consanguineous population. In probands with CHD who were consecutively recruited, genetic analysis was conducted based on the most likely etiology to either copy number variants (CNVs) analysis, multigene panel, whole exome sequencing (WES), or whole genome sequencing (WGS). A total of 201 families were recruited, of whom 59.7% were consanguineous. The overall diagnostic yield of genetic testing was 34.8%, with significantly higher yield in syndromic compared to isolated CHD (48.8% vs. 11.8%, respectively, ***\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Pathogenic CNV were identified in 12.4% and single\u2010nucleotides variants in 22.4%, with biallelic variants in only 6.5% of probands. In negative cases, analysis of WES\/WGS data did not reveal plausible variants. The tremendous genetic heterogeneity with a minority of homozygous variants in our cohort suggests that RG may be considered a rare cause of CHD even in consanguineous population. Our findings support the integration of next\u2010generation sequencing into routine clinical care of CHD and provide relevant ingredients for genetic counseling in consanguineous population.\n                  <\/jats:p>","DOI":"10.1111\/cge.70250","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:02:47Z","timestamp":1791468167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of Genomic Testing of Congenital Heart Disease in a Cohort From a Consanguineous Population"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4613-0945","authenticated-orcid":false,"given":"Abeer","family":"Almostafa","sequence":"first","affiliation":[{"name":"Cardiovascular Genomics Program Genomic Medicine Center of Excellence  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2506-9384","authenticated-orcid":false,"given":"Maarab","family":"Al\u2010Korashy","sequence":"additional","affiliation":[{"name":"Cardiovascular Genomics Program Genomic Medicine Center of Excellence  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarghuna","family":"Shinwari","sequence":"additional","affiliation":[{"name":"Cardiovascular Genomics Program Genomic Medicine Center of Excellence  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saud","family":"Takroni","sequence":"additional","affiliation":[{"name":"Cardiovascular Genomics Program Genomic Medicine Center of Excellence  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3031-6669","authenticated-orcid":false,"given":"Sahar","family":"Tulbah","sequence":"additional","affiliation":[{"name":"Cardiovascular Genomics Program Genomic Medicine Center of Excellence  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2157-9900","authenticated-orcid":false,"given":"Nadiah","family":"Al\u2010Ruwaili","sequence":"additional","affiliation":[{"name":"Heart Center of Excellence King Faisal Specialist Hospital &amp; Research Center (KFSH&amp;RC)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0801-6295","authenticated-orcid":false,"given":"Aisha","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Cardiovascular Genomics Program Genomic Medicine Center of Excellence  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faten","family":"AlHadheq","sequence":"additional","affiliation":[{"name":"Cardiovascular Genomics Program Genomic Medicine Center of Excellence  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeel","family":"Binomar","sequence":"additional","affiliation":[{"name":"Cardiovascular Genomics Program Genomic Medicine Center of Excellence  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"AlDowaihi","sequence":"additional","affiliation":[{"name":"Heart Center of Excellence King Faisal Specialist Hospital &amp; Research Center (KFSH&amp;RC)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9670-2087","authenticated-orcid":false,"given":"Hamzah","family":"Naji","sequence":"additional","affiliation":[{"name":"Cardiovascular Genomics Program Genomic Medicine Center of Excellence  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7037-6906","authenticated-orcid":false,"given":"Waleed","family":"Manea","sequence":"additional","affiliation":[{"name":"Heart Center of Excellence King Faisal Specialist Hospital &amp; Research Center (KFSH&amp;RC)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Alwadai","sequence":"additional","affiliation":[{"name":"Heart Failure &amp; Transplant Program Prince Sultan Cardiac Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5101-6905","authenticated-orcid":false,"given":"Dimpna C.","family":"Albert Brotons","sequence":"additional","affiliation":[{"name":"Heart Center of Excellence King Faisal Specialist Hospital &amp; Research Center (KFSH&amp;RC)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4530-146X","authenticated-orcid":false,"given":"Abdulaziz","family":"Alfadley","sequence":"additional","affiliation":[{"name":"King Fahd University Hospital  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"AlQwaee","sequence":"additional","affiliation":[{"name":"Prince Sultan Cardiac Center  Buraydah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amani","family":"Othman","sequence":"additional","affiliation":[{"name":"Prince Sultan Cardiac Center  Buraydah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Alhuzaimi","sequence":"additional","affiliation":[{"name":"Heart Center of Excellence King Faisal Specialist Hospital &amp; Research Center (KFSH&amp;RC)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saud","family":"Aloufi","sequence":"additional","affiliation":[{"name":"Heart Center of Excellence King Faisal Specialist Hospital &amp; Research Center (KFSH&amp;RC)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghassan","family":"Siblini","sequence":"additional","affiliation":[{"name":"Heart Center of Excellence King Faisal Specialist Hospital &amp; Research Center (KFSH&amp;RC)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadel","family":"Alfadley","sequence":"additional","affiliation":[{"name":"Heart Center of Excellence King Faisal Specialist Hospital &amp; Research Center (KFSH&amp;RC)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Alsehly","sequence":"additional","affiliation":[{"name":"Heart Center of Excellence King Faisal Specialist Hospital &amp; Research Center (KFSH&amp;RC)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7261-6750","authenticated-orcid":false,"given":"Mohammed","family":"Alhabdan","sequence":"additional","affiliation":[{"name":"Heart Center of Excellence King Faisal Specialist Hospital &amp; Research Center (KFSH&amp;RC)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6083-2744","authenticated-orcid":false,"given":"Ali","family":"Alakhfash","sequence":"additional","affiliation":[{"name":"Prince Sultan Cardiac Center  Buraydah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansour","family":"Aljoufan","sequence":"additional","affiliation":[{"name":"Heart Center of Excellence King Faisal Specialist Hospital &amp; Research Center (KFSH&amp;RC)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Almesned","sequence":"additional","affiliation":[{"name":"Prince Sultan Cardiac Center  Buraydah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohair","family":"Alhalees","sequence":"additional","affiliation":[{"name":"Heart Center of Excellence King Faisal Specialist Hospital &amp; Research Center (KFSH&amp;RC)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7173-2044","authenticated-orcid":false,"given":"Zuhair","family":"Al\u2010Hassnan","sequence":"additional","affiliation":[{"name":"Cardiovascular Genomics Program Genomic Medicine Center of Excellence  Riyadh Saudi Arabia"},{"name":"Alfaisal University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"issue":"12","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1016\/S0735-1097(02)01886-7","article-title":"The Incidence of Congenital Heart Disease","volume":"39","author":"Hoffman J. I.","year":"2002","journal-title":"Journal of the American College of Cardiology"},{"issue":"2","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/ije\/dyz009","article-title":"Global Birth Prevalence of Congenital Heart Defects 1970\u20102017: Updated Systematic Review and Meta\u2010Analysis of 260 Studies","volume":"48","author":"Liu Y.","year":"2019","journal-title":"International Journal of Epidemiology"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0167-5273(97)00067-3","article-title":"Incidence of Congenital Heart Disease in Qatari Children","volume":"60","author":"Robida A.","year":"1997","journal-title":"International Journal of Cardiology"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1080\/02724936.2000.11748155","article-title":"Incidence and Spectrum of Congenital Heart Disease in Oman","volume":"20","author":"Subramanyan R.","year":"2000","journal-title":"Annals of Tropical Paediatrics"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2018-026351","article-title":"Congenital Anomalies and Associated Risk Factors in a Saudi Population: A Cohort Study From Pregnancy to Age 2\u2009Years","volume":"9","author":"Kurdi A. M.","year":"2019","journal-title":"BMJ Open"},{"issue":"3","key":"e_1_2_9_7_1","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a037234","article-title":"Environmental Risk Factors for Congenital Heart Disease","volume":"12","author":"Kalisch\u2010Smith J. I.","year":"2020","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"issue":"2","key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.clp.2015.02.009","article-title":"Genetics and Genetic Testing in Congenital Heart Disease","volume":"42","author":"Cowan J. R.","year":"2015","journal-title":"Clinics in Perinatology"},{"issue":"21","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"e653","DOI":"10.1161\/CIR.0000000000000606","article-title":"Genetic Basis for Congenital Heart Disease: Revisited: A Scientific Statement From the American Heart Association","volume":"138","author":"Pierpont M. E.","year":"2018","journal-title":"Circulation"},{"issue":"7453","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/nature12141","article-title":"De Novo Mutations in Histone\u2010Modifying Genes in Congenital Heart Disease","volume":"498","author":"Zaidi S.","year":"2013","journal-title":"Nature"},{"issue":"11","key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1038\/ng.3970","article-title":"Contribution of Rare Inherited and de Novo Variants in 2,871 Congenital Heart Disease Probands","volume":"49","author":"Jin S. C.","year":"2017","journal-title":"Nature Genetics"},{"issue":"8","key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/s41588-020-0652-z","article-title":"Genomic Analyses Implicate Noncoding de Novo Variants in Congenital Heart Disease","volume":"52","author":"Richter F.","year":"2020","journal-title":"Nature Genetics"},{"issue":"1","key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41525-021-00192-x","article-title":"Rapid Whole Genome Sequencing Impacts Care and Resource Utilization in Infants With Congenital Heart Disease","volume":"6","author":"Sweeney N. M.","year":"2021","journal-title":"npj Genomic Medicine"},{"issue":"6","key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/s41436-020-0757-x","article-title":"The Cardiac Genome Clinic: Implementing Genome Sequencing in Pediatric Heart Disease","volume":"22","author":"Reuter M. S.","year":"2020","journal-title":"Genetics in Medicine"},{"issue":"5","key":"e_1_2_9_15_1","first-page":"415","article-title":"Implementation of Rapid Genome Sequencing for Critically Ill Infants With Complex Congenital Heart Disease","volume":"16","author":"Hays T.","year":"2023","journal-title":"Circulation: Genomic and Precision Medicine"},{"issue":"2","key":"e_1_2_9_16_1","first-page":"69","article-title":"First\u2010Cousin Matings and Congenital Heart Disease in Saudi Arabia","volume":"2","author":"Becker S.","year":"2000","journal-title":"Public Health Genomics"},{"issue":"1","key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/1096-8628(20010215)99:1<8::AID-AJMG1116>3.0.CO;2-U","article-title":"Consanguinity and Congenital Heart Disease in Saudi Arabia","volume":"99","author":"Becker S. M.","year":"2001","journal-title":"American Journal of Medical Genetics"},{"issue":"4","key":"e_1_2_9_18_1","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1017\/S1047951107000704","article-title":"Congenital Cardiac Disease and Inbreeding: Specific Defects Escape Higher Risk due to Parental Consanguinity","volume":"17","author":"Chehab G.","year":"2007","journal-title":"Cardiology in the Young"},{"issue":"8","key":"e_1_2_9_19_1","doi-asserted-by":"crossref","DOI":"10.3390\/genes13081369","article-title":"Investigation of Genetic Causes in Patients With Congenital Heart Disease in Qatar: Findings From the Sidra Cardiac Registry","volume":"13","author":"Okashah S.","year":"2022","journal-title":"Genes"},{"issue":"10","key":"e_1_2_9_20_1","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2419992122","article-title":"Recessive Genetic Contribution to Congenital Heart Disease in 5,424 Probands","volume":"122","author":"Dong W.","year":"2025","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","DOI":"10.1002\/mgg3.1944","article-title":"Mutation Spectrum of Congenital Heart Disease in a Consanguineous Turkish Population","volume":"10","author":"Dong W.","year":"2022","journal-title":"Molecular Genetics & Genomic Medicine"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70250","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70250","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70250","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:02:50Z","timestamp":1791468170000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":20,"alternative-id":["10.1111\/cge.70250"],"URL":"https:\/\/doi.org\/10.1111\/cge.70250","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]},"assertion":[{"value":"2025-11-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cge.70250"}}