Journal article
TBX3 and EFNA4 Variant in a Family with Ulnar-Mammary Syndrome and Sagittal Craniosynostosis
Genes, Vol.13(9), 1649
09/14/2022
DOI: 10.3390/genes13091649
PMCID: PMC9498434
PMID: 36140816
Abstract
Case report.
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 > A, IVS3 + 1G > A). This variant was inherited from the proband’s father who was also diagnosed with UMS with the additional clinical finding of congenital, sagittal craniosynostosis. Subsequent whole genome analysis in the proband’s father detected a variant in the EFNA4 gene (c.178C > 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.
Details
- Title: Subtitle
- TBX3 and EFNA4 Variant in a Family with Ulnar-Mammary Syndrome and Sagittal Craniosynostosis
- Creators
- Moon Ley Tung - National University of SingaporeBharatendu Chandra - National University of SingaporeJaclyn Kotlarek - Roy J. and Lucille A. Carver College of MedicineMarcelo Melo - Roy J. and Lucille A. Carver College of MedicineElizabeth Phillippi - Roy J. and Lucille A. Carver College of MedicineCristina M Justice - National Human Genome Research InstituteAnthony Musolf - National Human Genome Research InstituteSimeon A Boyadijev - University of California, DavisPaul A Romitti - University of IowaBenjamin Darbro - Roy J. and Lucille A. Carver College of MedicineHatem El-Shanti - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Genes, Vol.13(9), 1649
- DOI
- 10.3390/genes13091649
- PMID
- 36140816
- PMCID
- PMC9498434
- NLM abbreviation
- Genes (Basel)
- eISSN
- 2073-4425
- ISSN
- 2073-4425
- eISSN
- 2073-4425
- Grant note
- DOI: 10.13039/100008893, name: University of Iowa, award: Internal Funding by the University of Iowa
- Language
- English
- Date published
- 09/14/2022
- Academic Unit
- Stead Family Department of Pediatrics; Epidemiology; Biostatistics; Medical Genetics and Genomics
- Record Identifier
- 9984297352302771
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