{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:50:03Z","timestamp":1777078203674,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC1005304"],"award-info":[{"award-number":["2021YFC1005304"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mandibulofacial dysostosis with microcephaly (MFDM) is a rare multiple malformation syndrome characterized by malar and mandibular hypoplasia and congenital\u2010 or postnatal\u2010onset microcephaly induced by haploinsufficiency of (elongation factor Tu GTP\u2010binding domain\u2010containing 2) <jats:italic>EFTUD2<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report the case of a 16\u2010month\u2010old boy with MFDM symptoms, including malar and mandibular hypoplasia, microcephaly, micrognathia, midline cleft palate, microtia, auditory canal atresia, severe sensorineural hearing loss, and developmental delay. Whole\u2010exome sequencing (WES) analysis of the patient's family was performed to identify the genetic etiology responsible for this phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a novel <jats:italic>de novo<\/jats:italic> missense mutation (c.671G&gt;T, p.Gly224Val) in the <jats:italic>EFTUD2<\/jats:italic>. According to the American College of Medical Genetics and Genomics (ACMG) 2015\u00a0guidelines, the c.671G&gt;T mutation was classified as likely pathogenic (PS2, PM1, PM2, and PP3). Based on our findings, prenatal diagnosis was performed on the second baby of the proband's parents to exclude the mutation and it was confirmed that the baby did not have the MFDM phenotype after 14\u00a0months of follow\u2010up. Furthermore, the zebrafish model confirmed that the <jats:italic>EFTUD2<\/jats:italic> c.671G&gt;T mutation caused a loss of gene function in EFTUD2, and the pathogenicity of the <jats:italic>EFTUD2<\/jats:italic> c.671G&gt;T mutation was classified as pathogenic (PS2, PS3, PM1, and PM2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate that WES is a useful tool for identifying potentially pathogenic mutations, particularly in rare disorders, and is advantageous for genetic counseling and subsequent prenatal diagnosis. Moreover, the importance of functional assays cannot be underestimated, which could further confirm the pathogenicity of the genetic variants.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24440","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T11:20:35Z","timestamp":1650280835000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A novel de <i>novo<\/i> missense mutation in <i>EFTUD2<\/i> identified by whole\u2010exome sequencing in mandibulofacial dysostosis with microcephaly"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6200-5865","authenticated-orcid":false,"given":"Mei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Medical Genetics West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0894-9344","authenticated-orcid":false,"given":"Yanyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu China"},{"name":"SCU\u2010CUHK Joint Laboratory for Reproductive Medicine West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Department of Pediatrics West China Second University Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4548-4657","authenticated-orcid":false,"given":"Huaqin","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu China"},{"name":"SCU\u2010CUHK Joint Laboratory for Reproductive Medicine West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Department of Pediatrics West China Second University Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4642-3848","authenticated-orcid":false,"given":"Ting","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,4,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22924"},{"key":"e_1_2_11_3_1","volume-title":"Mandibulofacial Dysostosis with Microcephaly. 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