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A novel missense mutation in the transcription factor FOXF1 co-segregating with infantile hypertrophic pyloric stenosis in the extended pedigree linked to IHPS5 on chromosome 16q24.

Everett, KV; Ataliotis, P; Chioza, BA; Shaw-Smith, C; Chung, EM (2017) A novel missense mutation in the transcription factor FOXF1 co-segregating with infantile hypertrophic pyloric stenosis in the extended pedigree linked to IHPS5 on chromosome 16q24. Pediatric Research, 81 (4). pp. 632-638. ISSN 1530-0447 https://doi.org/10.1038/pr.2016.244
SGUL Authors: Ataliotis, Paris Everett, Kate Victoria

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Abstract

BACKGROUND: The aim was to identify susceptibility alleles for infantile hypertrophic pyloric stenosis (IHPS) in a pedigree previously linked to IHPS5 on chromosome 16q24. METHODS: We screened the positional and functional candidate gene FOXF1 by Sanger sequencing in a single affected individual. All family members for whom DNA was available were genotyped to determine co-segregation status of the putative causal variant. Immunofluorescence studies were performed to compare the cellular localisation of wildtype and mutant form of the protein. Transcriptional activity was compared using a luciferase assay. RESULTS: A single novel substitution in FOXF1 (c.416G>A) predicted to result in a missense mutation (R139Q) was shown to co-segregate with disease trait. It was not seen in 560 control chromosomes nor has it been reported in ExAC or ESP. The R139Q substitution affects a conserved arginine residue within the DNA-binding domain of FOXF1. The transcriptional activity of the mutant FOXF1 protein is significantly reduced in comparison to wild-type. CONCLUSION: These results provide strong evidence that the R139Q substitution in FOXF1 causes IHPS in this family and imply a novel pathological pathway for the condition. They further support a role for FOXF1 in the regulation of embryonic and neonatal development of the gastro-intestinal tract.

Item Type: Article
Additional Information: © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Keywords: Pediatrics, 1114 Paediatrics And Reproductive Medicine
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: Pediatric Research
ISSN: 1530-0447
Language: ENG
Dates:
DateEvent
April 2017Published
17 November 2016Published Online
19 September 2016Accepted
Publisher License: Publisher's own licence
PubMed ID: 27855150
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/108416
Publisher's version: https://doi.org/10.1038/pr.2016.244

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