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Anorectal malformation associated with a mutation in the P63 gene in a family with split hand–foot malformation
PURPOSE: The aims of this study were to identify the mutation gene of a Chinese family with anorectal malformation (ARM) associated with split hand–foot malformation and to determine the spatiotemporal expression of the mutated gene during hindgut and anorectum development in human embryos. METHOD:...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898126/ https://www.ncbi.nlm.nih.gov/pubmed/23736768 http://dx.doi.org/10.1007/s00384-013-1725-6 |
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author | Su, Pengjun Yuan, Yuhang Huang, Ying Wang, Weilin Zhang, Zhibo |
author_facet | Su, Pengjun Yuan, Yuhang Huang, Ying Wang, Weilin Zhang, Zhibo |
author_sort | Su, Pengjun |
collection | PubMed |
description | PURPOSE: The aims of this study were to identify the mutation gene of a Chinese family with anorectal malformation (ARM) associated with split hand–foot malformation and to determine the spatiotemporal expression of the mutated gene during hindgut and anorectum development in human embryos. METHOD: A Chinese family with intrafamilial clinically variable manifestation was analyzed and primers were designed for exons 3–14 of P63, DLX5, DLX6, DAC, and HOXD13 as candidate genes and direct sequence analysis of the exons was performed. Immunohistochemical study of mutated gene in the hindgut and anorectum of human embryos of 4th–10th weeks was performed. RESULT: Affected individuals were found to have an Arg227Gln P63 gene mutation. From the 4th–10th weeks of gestation of the human embryo, the P63-positive cells were mainly located on the epithelium of the apical urorectal septum, hindgut, and cloacal membrane. After the anorectum ruptured during the 8th week, the P63 remained strongly immunoreactive on the epithelium of the anal canal and urethra, but the mucous membrane of the rectum exhibited no reaction. CONCLUSIONS: The mutation identified strongly suggests a causal relationship between the ARM phenotype and P63. The expression of P63 was persistently active during the dynamic and incessant septation of the cloaca and hindgut, suggesting that P63 may play a pivotal role in the morphogenesis of the hindgut and anorectum. |
format | Online Article Text |
id | pubmed-3898126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-38981262014-01-28 Anorectal malformation associated with a mutation in the P63 gene in a family with split hand–foot malformation Su, Pengjun Yuan, Yuhang Huang, Ying Wang, Weilin Zhang, Zhibo Int J Colorectal Dis Original Article PURPOSE: The aims of this study were to identify the mutation gene of a Chinese family with anorectal malformation (ARM) associated with split hand–foot malformation and to determine the spatiotemporal expression of the mutated gene during hindgut and anorectum development in human embryos. METHOD: A Chinese family with intrafamilial clinically variable manifestation was analyzed and primers were designed for exons 3–14 of P63, DLX5, DLX6, DAC, and HOXD13 as candidate genes and direct sequence analysis of the exons was performed. Immunohistochemical study of mutated gene in the hindgut and anorectum of human embryos of 4th–10th weeks was performed. RESULT: Affected individuals were found to have an Arg227Gln P63 gene mutation. From the 4th–10th weeks of gestation of the human embryo, the P63-positive cells were mainly located on the epithelium of the apical urorectal septum, hindgut, and cloacal membrane. After the anorectum ruptured during the 8th week, the P63 remained strongly immunoreactive on the epithelium of the anal canal and urethra, but the mucous membrane of the rectum exhibited no reaction. CONCLUSIONS: The mutation identified strongly suggests a causal relationship between the ARM phenotype and P63. The expression of P63 was persistently active during the dynamic and incessant septation of the cloaca and hindgut, suggesting that P63 may play a pivotal role in the morphogenesis of the hindgut and anorectum. Springer Berlin Heidelberg 2013-06-05 2013 /pmc/articles/PMC3898126/ /pubmed/23736768 http://dx.doi.org/10.1007/s00384-013-1725-6 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by-nc/2.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Article Su, Pengjun Yuan, Yuhang Huang, Ying Wang, Weilin Zhang, Zhibo Anorectal malformation associated with a mutation in the P63 gene in a family with split hand–foot malformation |
title | Anorectal malformation associated with a mutation in the P63 gene in a family with split hand–foot malformation |
title_full | Anorectal malformation associated with a mutation in the P63 gene in a family with split hand–foot malformation |
title_fullStr | Anorectal malformation associated with a mutation in the P63 gene in a family with split hand–foot malformation |
title_full_unstemmed | Anorectal malformation associated with a mutation in the P63 gene in a family with split hand–foot malformation |
title_short | Anorectal malformation associated with a mutation in the P63 gene in a family with split hand–foot malformation |
title_sort | anorectal malformation associated with a mutation in the p63 gene in a family with split hand–foot malformation |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898126/ https://www.ncbi.nlm.nih.gov/pubmed/23736768 http://dx.doi.org/10.1007/s00384-013-1725-6 |
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