Monoallelic Loss-of-Function IFT140 Pathogenic Variants Cause Autosomal Dominant Polycystic Kidney Disease: A Confirmatory Study With Suspicion of an Additional Cardiac Phenotype.

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 6 non-family-related cases of monoallelic IFT140 LoF variants, identified from 1,340 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 pathologic frameshift IFT140 variation. As well as this particular Mainzer-Saldino case, our 6 additional patients confirm that heterozygous IFT140 frameshift variants are responsible for the cystic phenotype and kidney failure. Interestingly, of the 6 patients, 2 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.

[Eosinophiluria: accreditation with establishment of an inter-laboratories exchange]. / Éosinophilurie : accréditation avec mise en place d'un échange inter-laboratoires.

Eosinophiluria corresponds to search eosinophils in urine. These are normally absent in urine, their presence could be associated with different clinical conditions affecting kidney or urinary tract. This analysis of medical biology laboratory listed in the French Nomenclature of acts of medical biology has to be validated according to norm NF EN ISO 15189. The principle of eosinophiluria method is based on eosinophils quantification by optical microscopy in a urine sample (urination) after staining. The aim of this article is to provide to biologists the eosinophiluria's clinical interest, but also bibliographic, technical and practical elements that can help them to establish eosinophiluria in their laboratories. The method validation elements were described for each item of SH Form 43. They include the analysis risks study, inter-operator variability, uncertainties, measurement range, comparison of methods based on the comparison of two staining, interferences, robustness, reliability of reagents, reference interval. Regarding accuracy, in absence of external quality assessment for this analysis, an inter-laboratory exchange has been set up in accordance with the requirements of the norm. Its organization is described. The performance of eosinophiluria was verified, recalling the importance of the pre-analytical conditions and the quality of staining. All of these data are presented and led the accreditation of eosinophiluria in our laboratory.