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Clinical and genetic analysis in Chinese families with synpolydactyly, and cellular localization of HOXD13 with different length of polyalanine tract

Synpolydactyly (SPD) is caused by mutations in the transcription factor gene HOXD13. Such mutations include polyalanine expansion (PAE), but further study is required for the phenotypic spectrum characteristics of HOXD13 PAE. We investigated four unrelated Chinese families with significant limb malf...

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Autores principales: Chen, Xiumin, Zhao, Feiyue, Xu, Yiming, Cao, Yixuan, Li, Shan, Zhang, Xue, Zhao, Xiuli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10073534/
https://www.ncbi.nlm.nih.gov/pubmed/37035736
http://dx.doi.org/10.3389/fgene.2023.1105046
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author Chen, Xiumin
Zhao, Feiyue
Xu, Yiming
Cao, Yixuan
Li, Shan
Zhang, Xue
Zhao, Xiuli
author_facet Chen, Xiumin
Zhao, Feiyue
Xu, Yiming
Cao, Yixuan
Li, Shan
Zhang, Xue
Zhao, Xiuli
author_sort Chen, Xiumin
collection PubMed
description Synpolydactyly (SPD) is caused by mutations in the transcription factor gene HOXD13. Such mutations include polyalanine expansion (PAE), but further study is required for the phenotypic spectrum characteristics of HOXD13 PAE. We investigated four unrelated Chinese families with significant limb malformations. Three PAEs were found in the HOXD13 polyalanine coding region: c.172_192dup (p.Ala58_Ala64dup) in Family 1, c.169_192dup (p.Ala57_Ala64dup) in Family 2, and c.183_210dup (p.Ala62_Ala70dup) in Family 3 and Family 4. Interestingly, we identified a new manifestation of preaxial polydactyly in both hands in a pediatric patient with an expansion of seven alanines, a phenotype not previously noted in SPD patients. Comparing with the wild-type cells and mutant cells with polyalanine contractions (PACs), the HOXD13 protein with a PAE of nine-alanine or more was difficult to enter the nucleus, and easy to form inclusion bodies in the cytoplasm, and with the increase of PAE, the more inclusion bodies were formed. This study not only expanded the phenotypic spectrum of SPD, but also enriched our understanding of its pathogenic mechanisms.
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spelling pubmed-100735342023-04-06 Clinical and genetic analysis in Chinese families with synpolydactyly, and cellular localization of HOXD13 with different length of polyalanine tract Chen, Xiumin Zhao, Feiyue Xu, Yiming Cao, Yixuan Li, Shan Zhang, Xue Zhao, Xiuli Front Genet Genetics Synpolydactyly (SPD) is caused by mutations in the transcription factor gene HOXD13. Such mutations include polyalanine expansion (PAE), but further study is required for the phenotypic spectrum characteristics of HOXD13 PAE. We investigated four unrelated Chinese families with significant limb malformations. Three PAEs were found in the HOXD13 polyalanine coding region: c.172_192dup (p.Ala58_Ala64dup) in Family 1, c.169_192dup (p.Ala57_Ala64dup) in Family 2, and c.183_210dup (p.Ala62_Ala70dup) in Family 3 and Family 4. Interestingly, we identified a new manifestation of preaxial polydactyly in both hands in a pediatric patient with an expansion of seven alanines, a phenotype not previously noted in SPD patients. Comparing with the wild-type cells and mutant cells with polyalanine contractions (PACs), the HOXD13 protein with a PAE of nine-alanine or more was difficult to enter the nucleus, and easy to form inclusion bodies in the cytoplasm, and with the increase of PAE, the more inclusion bodies were formed. This study not only expanded the phenotypic spectrum of SPD, but also enriched our understanding of its pathogenic mechanisms. Frontiers Media S.A. 2023-03-22 /pmc/articles/PMC10073534/ /pubmed/37035736 http://dx.doi.org/10.3389/fgene.2023.1105046 Text en Copyright © 2023 Chen, Zhao, Xu, Cao, Li, Zhang and Zhao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Chen, Xiumin
Zhao, Feiyue
Xu, Yiming
Cao, Yixuan
Li, Shan
Zhang, Xue
Zhao, Xiuli
Clinical and genetic analysis in Chinese families with synpolydactyly, and cellular localization of HOXD13 with different length of polyalanine tract
title Clinical and genetic analysis in Chinese families with synpolydactyly, and cellular localization of HOXD13 with different length of polyalanine tract
title_full Clinical and genetic analysis in Chinese families with synpolydactyly, and cellular localization of HOXD13 with different length of polyalanine tract
title_fullStr Clinical and genetic analysis in Chinese families with synpolydactyly, and cellular localization of HOXD13 with different length of polyalanine tract
title_full_unstemmed Clinical and genetic analysis in Chinese families with synpolydactyly, and cellular localization of HOXD13 with different length of polyalanine tract
title_short Clinical and genetic analysis in Chinese families with synpolydactyly, and cellular localization of HOXD13 with different length of polyalanine tract
title_sort clinical and genetic analysis in chinese families with synpolydactyly, and cellular localization of hoxd13 with different length of polyalanine tract
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10073534/
https://www.ncbi.nlm.nih.gov/pubmed/37035736
http://dx.doi.org/10.3389/fgene.2023.1105046
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