An example of parenchymal renal sparing in the context of complex malformations due to a novel mutation in the PBX1 gene.
CAKUT
PBX1
WES
development
homeodomain
kidney
Journal
Birth defects research
ISSN: 2472-1727
Titre abrégé: Birth Defects Res
Pays: United States
ID NLM: 101701004
Informations de publication
Date de publication:
15 07 2022
15 07 2022
Historique:
revised:
31
05
2022
received:
30
03
2022
accepted:
06
06
2022
pubmed:
26
6
2022
medline:
19
7
2022
entrez:
25
6
2022
Statut:
ppublish
Résumé
PBX1 encodes the pre-B cell leukemia factor 1, a Three Amino acid Loop Extension (TALE) transcription factor crucial to regulate basic developmental processes. PBX1 loss-of-function variants have been initially described in association with renal malformations in both isolated and syndromic forms. Herein, we report a male infant presenting multiple organ malformations (cleidosternal dysostosis, micrognathia, left lung hypoplasia, wide interatrial defect, pulmonary hypertension, total anomalous pulmonary venous return, intestinal malrotation) and carrying the heterozygous de novo c.868C > T (p.Arg290Trp) variant in PBX1. This novel variant affects the highly conserved homeodomain of the protein, leading to a non-conservative substitution and consequently altering its tridimensional structure and DNA-binding capacity. So far, PBX1 has been reported in association with a broad spectrum of renal anomalies. However, given the role of this gene in many different developing processes, whole-exome sequencing can detect mutations in PBX1 even in patients with different phenotypes, not necessarily involving the renal primordium. This report presents a novel PBX1 variant with a predicted strong deleterious effect. The mutation leads to a non-conservative substitution in a very highly conserved domain of the protein, thus altering its tertiary structure and DNA-binding capacity.
Substances chimiques
DNA-Binding Proteins
0
Pre-B-Cell Leukemia Transcription Factor 1
0
PBX1 protein, human
0
DNA
9007-49-2
Types de publication
Case Reports
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
674-681Informations de copyright
© 2022 Wiley Periodicals LLC.
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