{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T15:57:59Z","timestamp":1772467079029,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Medical Practice Plan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Goldenhar syndrome (oculo\u2013auriculo\u2013vertebral spectrum, OAVS) is a rare congenital disorder characterized by craniofacial malformations, systemic anomalies, and significant phenotypic variability. Although it is the second most common craniofacial malformation after a cleft palate, the genetic etiology of Goldenhar syndrome remains largely unexplored. This study aimed to identify genetic variants contributing to Goldenhar syndrome in a Lebanese family with three affected individuals, using whole-exome sequencing and complementary genomic approaches. Methods: Whole-exome sequencing was performed on the nuclear family to identify variants associated with the syndrome. Complementary DNA methylation and gene ontology analyses were conducted to explore epigenetic modifications. Results: A missense shared variant in the MID1 between the affected individuals [NP_000372.1): p. Ile593Phe] gene was observed in the family, while current ACMG evidence was insufficient to establish causality. Additional variants were identified, including a de novo mutation in FBXW11 and a rare frameshift alteration in NDUFAF8, with limited segregation, implicating these genes in associated phenotypes such as craniofacial anomalies and cardiac defects. DNA methylation analysis revealed hypomethylation at CpG sites within the ZC3H3 gene, suggesting an epigenetic contribution to disease variability. Conclusions: Our findings underscore the genetic and epigenetic complexity of Goldenhar syndrome, providing new insights into its molecular etiology and highlighting the challenges of variant interpretation in familial cases of rare congenital disorders.<\/jats:p>","DOI":"10.3390\/genes17030299","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T14:55:01Z","timestamp":1772463301000},"page":"299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of a Familial Goldenhar Syndrome Case Using Whole-Exome Sequencing"],"prefix":"10.3390","volume":"17","author":[{"given":"Yosra","family":"Bejaoui","sequence":"first","affiliation":[{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"},{"name":"Weill Cornell Medicine, Doha P.O. Box 24144, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1505-6360","authenticated-orcid":false,"given":"Yasser","family":"Al-Sarraj","sequence":"additional","affiliation":[{"name":"Qatar Genome Program (QGP), Qatar Foundation Research, Development and Innovation, Qatar Foundation (QF), Doha P.O. Box 5825, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Al-Hage","sequence":"additional","affiliation":[{"name":"Department of Dermatology, American University of Beirut Medical Center, Beirut P.O. Box 11-0236, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fadi F.","family":"Bitar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut P.O. Box 11-0236, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nady","family":"El Hajj","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"},{"name":"College of Science and Engineering, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2157-5279","authenticated-orcid":false,"given":"Georges","family":"Nemer","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"},{"name":"Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut P.O. Box 11-0236, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mazen","family":"Kurban","sequence":"additional","affiliation":[{"name":"Department of Dermatology, American University of Beirut Medical Center, Beirut P.O. Box 11-0236, Lebanon"},{"name":"Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut P.O. Box 11-0236, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","unstructured":"Goldenhar, M. (1952). 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