{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T18:01:03Z","timestamp":1770919263339,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008893","name":"University of Iowa","doi-asserted-by":"publisher","award":["Internal Funding  by the University of Iowa"],"award-info":[{"award-number":["Internal Funding  by the University of Iowa"]}],"id":[{"id":"10.13039\/100008893","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Ulnar-mammary syndrome (UMS) is a rare, autosomal dominant disorder characterized by anomalies affecting the limbs, apocrine glands, dentition, and genital development. This syndrome is caused by haploinsufficiency in the T-Box3 gene (TBX3), with considerable variability in the clinical phenotype being observed even within families. We describe a one-year-old female with unilateral, postaxial polydactyly, and bilateral fifth fingernail duplication. Next-generation sequencing revealed a novel, likely pathogenic, variant predicted to affect the canonical splice site in intron 3 of the TBX3 gene (c.804 + 1G &gt; A, IVS3 + 1G &gt; A). This variant was inherited from the proband\u2019s father who was also diagnosed with UMS with the additional clinical finding of congenital, sagittal craniosynostosis. Subsequent whole genome analysis in the proband\u2019s father detected a variant in the EFNA4 gene (c.178C &gt; T, p.His60Tyr), which has only been reported to be associated with sagittal craniosynostosis in one patient prior to this report but reported in other cranial suture synostosis. The findings in this family extend the genotypic spectrum of UMS, as well as the phenotypic spectrum of EFNA4-related craniosynostosis.<\/jats:p>","DOI":"10.3390\/genes13091649","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T20:50:45Z","timestamp":1663188645000},"page":"1649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["TBX3 and EFNA4 Variant in a Family with Ulnar-Mammary Syndrome and Sagittal Craniosynostosis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5436-1720","authenticated-orcid":false,"given":"Moon Ley","family":"Tung","sequence":"first","affiliation":[{"name":"Stead Family Department of Pediatrics, Division of Medical Genetics and Genomics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA"},{"name":"Department of Medicine, National University of Singapore, Singapore 117597, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bharatendu","family":"Chandra","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics, Division of Medical Genetics and Genomics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA"},{"name":"Department of Medicine, National University of Singapore, Singapore 117597, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaclyn","family":"Kotlarek","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics, Division of Medical Genetics and Genomics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo","family":"Melo","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics, Division of Medical Genetics and Genomics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3270-7564","authenticated-orcid":false,"given":"Elizabeth","family":"Phillippi","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics, Division of Medical Genetics and Genomics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina M.","family":"Justice","sequence":"additional","affiliation":[{"name":"Genometrics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health (NIH), Baltimore, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Musolf","sequence":"additional","affiliation":[{"name":"Statistical Genetics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health (NIH), Baltimore, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simeon A.","family":"Boyadijev","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California Davis, Sacramento, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5393-9984","authenticated-orcid":false,"given":"Paul A.","family":"Romitti","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9279-356X","authenticated-orcid":false,"given":"Benjamin","family":"Darbro","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics, Division of Medical Genetics and Genomics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6230-8316","authenticated-orcid":false,"given":"Hatem","family":"El-Shanti","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics, Division of Medical Genetics and Genomics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103615","DOI":"10.1016\/j.ejmg.2019.01.005","article-title":"A de novo TBX3 mutation presenting as dorsalization of the little fingers: A forme fruste phenotype of ulnar-mammary syndrome","volume":"63","author":"Maddirevula","year":"2020","journal-title":"Eur. 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