{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:59:20Z","timestamp":1791197960831,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,6,27]],"date-time":"2015-06-27T00:00:00Z","timestamp":1435363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY015518"],"award-info":[{"award-number":["R01EY015518"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital microphthalmia and coloboma are severe developmental defects that are frequently associated with additional systemic anomalies and display a high level of genetic heterogeneity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To identify the pathogenic variant in a patient with microphthalmia, coloboma, retinal dystrophy, microcephaly, and other features, whole exome sequencing analysis of the patient and parental samples was undertaken. To further explore the identified variant\/gene, expression and functional studies in zebrafish were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Whole exome sequencing revealed a de novo variant, c.473_474delGA, p.(Arg158Lysfs*4), in <jats:italic>EFTUD2<\/jats:italic> which encodes a component of the spliceosome complex. Dominant mutations in <jats:italic>EFTUD2<\/jats:italic> cause Mandibulofacial Dysostosis, Guion\u2010Almeida type, which does not involve microphthalmia, coloboma, or retinal dystrophy; analysis of genes known to cause these ocular phenotypes identified several variants of unknown significance but no causal alleles in the affected patient. Zebrafish <jats:italic>eftud2<\/jats:italic> demonstrated high sequence conservation with the human gene and broad embryonic expression. TALEN\u2010mediated disruption was employed to generate a c.378_385 del, p.(Ser127Aspfs*23) truncation mutation in <jats:italic>eftud2<\/jats:italic>. Homozygous mutants displayed a reduced head size, small eye, curved body, and early embryonic lethality. Apoptosis assays demonstrated a striking increase in terminal deoxynucleotidyl transferase\u2013mediated deoxyuridine triphosphate nick end\u2010labeling (TUNEL)\u2010positive cells in the developing brain, eye, spinal cord, and other tissues starting at 30 hours postfertilization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study reports a novel mutation in <jats:italic>EFTUD2<\/jats:italic> in a Mandibulofacial Dysostosis, Guion\u2010Almeida type patient with unusual ocular features and the generation of a first animal model of <jats:italic>eftud2<\/jats:italic> deficiency. The severe embryonic phenotype observed in <jats:italic>eftud2<\/jats:italic> mutants indicates an important conserved role during development of diverse tissues in vertebrates. 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