Monoallelic Loss of Function IFT140 Pathogenic Variants Cause Autosomal Dominant Polycystic Kidney Disease: A Confirmatory Study With Suspicion of an Additional Cardiac Phenotype.
Fiche publication
Date publication
octobre 2023
Journal
American journal of kidney diseases : the official journal of the National Kidney Foundation
Auteurs
Membres identifiés du Cancéropôle Est :
Pr LEBRE Anne-Sophie
Tous les auteurs :
Salhi S, Doreille A, Dancer MS, Boueilh A, Filipozzi P, El Karoui K, Ponce F, Lebre AS, Raymond L, Mesnard L
Lien Pubmed
Résumé
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. While biallelic variants affecting IFT140 are responsible for Mainzer-Saldino syndrome (characterized by severe ciliopathy causing skeletal abnormalities, kidney disease and cysts), monoallelic loss of function (LoF) variants have been recently reported as an important cause of ADPKD beyond PKD1/2 genes. Herein, we report six non-family-related cases of monoallelic IFT140 LoF variants, identified from 1340 exomes sequenced for nephrological indications in our local database. Every patient presented with polycystic kidney disease. Furthermore, the mother of a boy diagnosed with Mainzer-Saldino syndrome with a biallelic variant affecting IFT140, presented with several bilateral cysts revealed after kidney imaging and was found to carry a pathological frameshift IFT140 variation. As well as this particular Mainzer-Saldino case, our six additional patients confirm that heterozygous IFT140 frameshift variants are responsible for the cystic phenotype and kidney failure. Interestingly, of the six patients, two also exhibited dilated cardiomyopathy which was of unknown origin as no genetic cause was found after exome sequencing analysis, suggesting a potential connection between IFT140 and heart disease.
Référence
Am J Kidney Dis. 2023 10 14;: