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TBX3 and EFNA4 Variant in a Family with Ulnar-Mammary Syndrome and Sagittal Craniosynostosis
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 be...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9498434/ https://www.ncbi.nlm.nih.gov/pubmed/36140816 http://dx.doi.org/10.3390/genes13091649 |
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author | Tung, Moon Ley Chandra, Bharatendu Kotlarek, Jaclyn Melo, Marcelo Phillippi, Elizabeth Justice, Cristina M. Musolf, Anthony Boyadijev, Simeon A. Romitti, Paul A. Darbro, Benjamin El-Shanti, Hatem |
author_facet | Tung, Moon Ley Chandra, Bharatendu Kotlarek, Jaclyn Melo, Marcelo Phillippi, Elizabeth Justice, Cristina M. Musolf, Anthony Boyadijev, Simeon A. Romitti, Paul A. Darbro, Benjamin El-Shanti, Hatem |
author_sort | Tung, Moon Ley |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9498434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94984342022-09-23 TBX3 and EFNA4 Variant in a Family with Ulnar-Mammary Syndrome and Sagittal Craniosynostosis Tung, Moon Ley Chandra, Bharatendu Kotlarek, Jaclyn Melo, Marcelo Phillippi, Elizabeth Justice, Cristina M. Musolf, Anthony Boyadijev, Simeon A. Romitti, Paul A. Darbro, Benjamin El-Shanti, Hatem Genes (Basel) 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. MDPI 2022-09-14 /pmc/articles/PMC9498434/ /pubmed/36140816 http://dx.doi.org/10.3390/genes13091649 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Case Report Tung, Moon Ley Chandra, Bharatendu Kotlarek, Jaclyn Melo, Marcelo Phillippi, Elizabeth Justice, Cristina M. Musolf, Anthony Boyadijev, Simeon A. Romitti, Paul A. Darbro, Benjamin El-Shanti, Hatem TBX3 and EFNA4 Variant in a Family with Ulnar-Mammary Syndrome and Sagittal Craniosynostosis |
title | TBX3 and EFNA4 Variant in a Family with Ulnar-Mammary Syndrome and Sagittal Craniosynostosis |
title_full | TBX3 and EFNA4 Variant in a Family with Ulnar-Mammary Syndrome and Sagittal Craniosynostosis |
title_fullStr | TBX3 and EFNA4 Variant in a Family with Ulnar-Mammary Syndrome and Sagittal Craniosynostosis |
title_full_unstemmed | TBX3 and EFNA4 Variant in a Family with Ulnar-Mammary Syndrome and Sagittal Craniosynostosis |
title_short | TBX3 and EFNA4 Variant in a Family with Ulnar-Mammary Syndrome and Sagittal Craniosynostosis |
title_sort | tbx3 and efna4 variant in a family with ulnar-mammary syndrome and sagittal craniosynostosis |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9498434/ https://www.ncbi.nlm.nih.gov/pubmed/36140816 http://dx.doi.org/10.3390/genes13091649 |
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