{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:55:28Z","timestamp":1792252528892,"version":"4.4.0"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"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"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Heterotaxy (HTX) is a group of clinical conditions with a shared pathology of dislocation of one or more organs along the left\u2013right axis. The etiology of HTX is tremendously heterogeneous spanning environmental factors, chromosomal aberrations, mono\/oligogenic variants, and complex inheritance. However, in the vast majority of cases, the etiology of HTX remains elusive. Here, we sought to describe the yield of genetic analysis and spectrum of variants in HTX in our highly consanguineous population. Twenty\u2010four affected individuals, from 19 unrelated families, were consecutively recruited. Genetic analysis, with exome sequencing, genome sequencing, or multigene panel, detected 9 unique variants, 7 of which were novel, in 8 genes known to be implicated in autosomal recessive form of HTX (\n                    <jats:italic>C1orf127<\/jats:italic>\n                    ,\n                    <jats:italic>CCDC39<\/jats:italic>\n                    ,\n                    <jats:italic>CIROP<\/jats:italic>\n                    ,\n                    <jats:italic>DNAAF3<\/jats:italic>\n                    ,\n                    <jats:italic>DNAH5<\/jats:italic>\n                    ,\n                    <jats:italic>DNAH9<\/jats:italic>\n                    ,\n                    <jats:italic>MMP21<\/jats:italic>\n                    , and\n                    <jats:italic>MNS1<\/jats:italic>\n                    ) providing a yield of 42.1%. Of note, 7 of the 9 variants were homozygous, while 2 were inherited in compound heterozygosity, including a heterozygous CNV deletion. A search for candidate genes in negative cases did not reveal a plausible variant. Our work demonstrates a relatively high yield of genetic testing in HTX in a consanguineous population with an enrichment of homozygous variants. The significant genetic heterogeneity observed herewith underscores the complex developmental mechanisms implicated in the pathogenesis of HTX and supports adopting a genome\u2010wide analysis in the diagnostic evaluation of HTX.\n                  <\/jats:p>","DOI":"10.1111\/cge.14641","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T05:34:28Z","timestamp":1731044068000},"page":"224-230","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genetic Analysis of Heterotaxy in a Consanguineous Cohort"],"prefix":"10.1111","volume":"107","author":[{"given":"Maarab","family":"Al\u2010Korashy","sequence":"first","affiliation":[{"name":"Center for Genomic Medicine  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeel","family":"Binomar","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer","family":"Al\u2010Mostafa","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Al\u2010Mogarri","sequence":"additional","affiliation":[{"name":"Pediatrics Department  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saud","family":"Al\u2010Oufi","sequence":"additional","affiliation":[{"name":"Heart Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Al\u2010Admawi","sequence":"additional","affiliation":[{"name":"Heart Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansour","family":"Al\u2010Jufan","sequence":"additional","affiliation":[{"name":"Heart Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najmeddine","family":"Echahidi","sequence":"additional","affiliation":[{"name":"Heart Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Mokeem","sequence":"additional","affiliation":[{"name":"Neuroscience Centre King Faisal Specialist Hospital &amp; Research Centre  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Alfares","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khushnooda","family":"Ramzan","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Tulbah","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha","family":"Al\u2010Qahtani","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saud","family":"Takroni","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sateesh","family":"Maddirevula","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhair","family":"Al\u2010Hassnan","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000606"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36695"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30228"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010022\u201002515\u20102"},{"key":"e_1_2_9_6_1","unstructured":"On line Mendelian Inheritance in Man (OMIM)\u00ae. McKusick\u2010Nathans Institute of Genetic Medicine Johns Hopkins University Baltimore MD accessed July 2024 www.omim.org."},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3970"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010018\u20100307\u2010z"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24132"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.32.8.623"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102021\u2010107775"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06045-0"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410\u2010248"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks53"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad989"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.112"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2015.0406"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1106"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007602"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14641","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T22:41:12Z","timestamp":1736721672000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,8]]},"references-count":18,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/cge.14641"],"URL":"https:\/\/doi.org\/10.1111\/cge.14641","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14641\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14641\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14641\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14641\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14641\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14641\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14641\/v2\/review1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,8]]},"assertion":[{"value":"2024-07-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}