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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:...

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Autores principales: Su, Pengjun, Yuan, Yuhang, Huang, Ying, Wang, Weilin, Zhang, Zhibo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2013
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.
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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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