Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784794757833162752
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
work_keys_str_mv AT tungmoonley tbx3andefna4variantinafamilywithulnarmammarysyndromeandsagittalcraniosynostosis
AT chandrabharatendu tbx3andefna4variantinafamilywithulnarmammarysyndromeandsagittalcraniosynostosis
AT kotlarekjaclyn tbx3andefna4variantinafamilywithulnarmammarysyndromeandsagittalcraniosynostosis
AT melomarcelo tbx3andefna4variantinafamilywithulnarmammarysyndromeandsagittalcraniosynostosis
AT phillippielizabeth tbx3andefna4variantinafamilywithulnarmammarysyndromeandsagittalcraniosynostosis
AT justicecristinam tbx3andefna4variantinafamilywithulnarmammarysyndromeandsagittalcraniosynostosis
AT musolfanthony tbx3andefna4variantinafamilywithulnarmammarysyndromeandsagittalcraniosynostosis
AT boyadijevsimeona tbx3andefna4variantinafamilywithulnarmammarysyndromeandsagittalcraniosynostosis
AT romittipaula tbx3andefna4variantinafamilywithulnarmammarysyndromeandsagittalcraniosynostosis
AT darbrobenjamin tbx3andefna4variantinafamilywithulnarmammarysyndromeandsagittalcraniosynostosis
AT elshantihatem tbx3andefna4variantinafamilywithulnarmammarysyndromeandsagittalcraniosynostosis