{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T05:07:41Z","timestamp":1779512861946,"version":"3.53.1"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"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":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cranioectodermal dysplasia (CED) is a rare autosomal recessive ciliopathy characterized by craniofacial, skeletal, and ectodermal anomalies. Significant phenotypic heterogeneity often results in clinical overlap with other skeletal dysplasias, including Robinow syndrome. In consanguineous populations, the presence of multiple rare variants can further complicate the molecular diagnosis. This study aimed to clarify the genetic basis of a complex syndromic presentation in a consanguineous Saudi family exhibiting features suggestive of both disorders using an integrated phenotypic, genomic, and computational approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Exome sequencing was performed on two affected siblings, followed by Sanger sequencing for the familial segregation analysis. Detailed phenotypic evaluation was combined with structural and bioinformatics analyses, including in silico pathogenicity prediction tools, three\u2010dimensional protein modeling, protein\u2013protein interaction analysis, and molecular docking to assess the structural and functional impact of candidate variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Exome sequencing identified a homozygous missense variant in\n                      <jats:italic>IFT122<\/jats:italic>\n                      gene (c.94G\u2009&gt;\u2009A; p.Gly32Arg), associated with cranioectodermal dysplasia 1, and a heterozygous frameshift variant in\n                      <jats:italic>DVL3<\/jats:italic>\n                      gene (c.1949_1950del; p.His650Profs*60), associated with Robinow syndrome. Segregation analysis excluded the\n                      <jats:italic>DVL3<\/jats:italic>\n                      variant as the primary cause, while the\n                      <jats:italic>IFT122<\/jats:italic>\n                      variant segregated with the phenotype in an autosomal recessive manner. Computational analyses demonstrated that the p.Gly32Arg substitution affects a highly conserved residue and is consistently predicted to be deleterious. Structural modeling revealed the disruption of local hydrogen bonding, increased solvent accessibility, and reduced protein stability. Protein\u2013protein interaction and molecular docking analyses further indicated altered interactions with key IFT\u2010A components, including TTC21B, IFT140, TULP3, and IFT43, suggesting impaired intraflagellar transport complex integrity and ciliary protein trafficking.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identifies a novel homozygous\n                      <jats:italic>IFT122<\/jats:italic>\n                      (c.94G\u2009&gt;\u2009A; p.Gly32Arg) variant underlying CED1, thereby expanding the molecular spectrum of\n                      <jats:italic>IFT122<\/jats:italic>\n                      \u2010related ciliopathies. These findings emphasize the value of integrating phenotypic, genomic, segregation, and structural analyses to resolve diagnostically challenging cases, particularly in consanguineous populations. Further functional studies are warranted to confirm this molecular mechanism.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70230","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T04:47:03Z","timestamp":1779079623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Level Genomic and Computational Analyses Identify a Novel\n                    <i>IFT122<\/i>\n                    Variant Associated With Cranioectodermal Dysplasia 1 in a Consanguineous Saudi Family"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0343-6083","authenticated-orcid":false,"given":"Deema","family":"Aljeaid","sequence":"first","affiliation":[{"name":"Department of Genetic Medicine, Faculty of Medicine King Abdulaziz University  Jeddah Saudi Arabia"},{"name":"Department of Genetic Medicine King Abdulaziz University Hospital  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4911-7277","authenticated-orcid":false,"given":"Abdulrahman","family":"Almadiny","sequence":"additional","affiliation":[{"name":"Madinah Health Cluster  Medina Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6727-4856","authenticated-orcid":false,"given":"Khalidah K.","family":"Nasser","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences King Abdulaziz University  Jeddah Saudi Arabia"},{"name":"Institute of Genomic Medicine Sciences (IGMS) King Abdulaziz University  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1312-6409","authenticated-orcid":false,"given":"Mahmoud","family":"Almutadares","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Faculty of Medicine King Abdulaziz University  Jeddah Saudi Arabia"},{"name":"Department of Genetic Medicine King Abdulaziz University Hospital  Jeddah Saudi Arabia"},{"name":"Department of Pediatrics Dr. Soliman Fakeeh Hospital, Fakeeh Care Group  Jeddah Saudi Arabia"},{"name":"Department of Clinical Sciences Fakeeh College of Medical Sciences, Fakeeh Care Group  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3850-707X","authenticated-orcid":false,"given":"Noha M.","family":"Issa","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Faculty of Medicine King Abdulaziz University  Jeddah Saudi Arabia"},{"name":"Department of Genetic Medicine King Abdulaziz University Hospital  Jeddah Saudi Arabia"},{"name":"Department of Human Genetics Medical Research Institute, Alexandria University  Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.09.10.612347"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.44"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.04.002"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.97"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2023.1243518"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2011.088864"},{"key":"e_1_2_12_8_1","volume-title":"GeneReviews","author":"Bacino C. 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