Fiche publication
Date publication
septembre 2019
Journal
Human mutation
Auteurs
Membres identifiés du Cancéropôle Est :
Dr POCH Olivier
Tous les auteurs :
Estrada-Cuzcano A, Etard C, Delvallée C, Stoetzel C, Schaefer E, Scheidecker S, Geoffroy V, Schneider A, Studer F, Mattioli F, Chennen K, Sigaudy S, Plassard D, Poch O, Piton A, Strahle U, Muller J, Dollfus H
Lien Pubmed
Résumé
Polydactyly is one of the most frequent inherited defects of the limbs characterized by supernumerary digits and high genetic heterogeneity. Among the many genes involved, either in isolated or syndromic forms, 8 have been implicated in postaxial polydactyly (PAP). Among those IQCE has been recently identified in a single consanguineous family. Using whole-exome sequencing in patients with uncharacterized ciliopathies including PAP, we identified 3 families with biallelic pathogenic variations in IQCE. Interestingly, the c.895_904del (p.Val301Serfs*8) was found in all families without sharing a common haplotype, suggesting a recurrent mechanism. Moreover, in 2 families, the systemic phenotype could be explained by additional pathogenic variants in known genes (TULP1, ATP6V1B1). RNA expression analysis on patients' fibroblasts confirms that dysfunction of IQCE leads to dysregulation of genes associated with the hedgehog-signaling pathway and zebrafish experiments demonstrate a full spectrum of phenotypes linked to defective cilia: body curvature, kidney cysts, left right asymmetry, misdirected cilia in pronephric duct and retinal defects. In conclusion, we identified 3 additional families confirming IQCE as a non-syndromic PAP gene. Our data emphasize, the importance of taking into account the complete set of variations of each individual as each clinical presentation could finally be explained by multiple genes. This article is protected by copyright. All rights reserved.
Mots clés
IQCE, RNA-seq, cilia, hedgehog signaling, polydactyly, zebrafish
Référence
Hum. Mutat.. 2019 Sep 24;:
