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International Journal of Colorectal Disease

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Open Access 01-12-2013 | Original Article

Anorectal malformation associated with a mutation in the P63 gene in a family with split hand–foot malformation

Authors: Pengjun Su, Yuhang Yuan, Ying Huang, Weilin Wang, Zhibo Zhang

Published in: International Journal of Colorectal Disease | Issue 12/2013

Abstract

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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Title: Anorectal malformation associated with a mutation in the P63 gene in a family with split hand–foot malformation
Authors: Pengjun Su
Yuhang Yuan
Ying Huang
Weilin Wang
Zhibo Zhang
Publication date: 01-12-2013
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Colorectal Disease / Issue 12/2013
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-013-1725-6

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Springer Medicine

Anorectal malformation associated with a mutation in the P63 gene in a family with split hand–foot malformation

Abstract

Purpose

Method

Result

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Method

Result

Conclusions

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