#4485 CLINICAL CASE OF MOSAICISM IN ADPKD PATIENT

Abstract

Abstract Background and Aims Autosomal Dominant Polycystic Kidney Disease (ADPKD) it's mainly characterized by renal involvement with progressive bilateral development of renal cysts and volumetric increase of the kidneys, responsible for the progressive loss of renal function that leads to chronic kidney disease (CKD) and the need of renal replacement therapy. There are some cases (doubtful, uncertain) in which it is necessary to perform genetic testing to achieve a definitive diagnosis. It looks like in ADPKD patients, mosaicism could modulate the clinical course of the disease. Mosaicism is characterized by few cell populations with different genomes. In these special cases the diagnosis is very difficult and the genetic analysis could be an important and helpful tool. With this report, we want to highlight the importance of the use of several diagnostic methods in those ‘atypical’ cases where otherwise the analysis would have been negative from a first molecular approach. Method A 47 years old woman came to our attention with typical picture of ADPKD, arterial hypertension and chronic kidney disease CKD (3b). She had no ADPKD family history, but since she had a son, genetic testing was performed. According to our workflow, first level analysis includes Next Generation Sequencing (NGS). Second level analysis, performed to investigate other genes and large rearrangement, was based on Multiplex Ligation-dependent Probe Amplification (MLPA) analysis of PKD1 and PKD2 genes, using Salsa MLPA ProbeMix P352 PKD1PKD2 kit and ProbeMix P351 PKD1 kit ©MRC Holland. Results NGS did not detect the presence of any genomic variants. Therefore, second-level genetic analysis (several approaches), showed a large deletion in heterozygosis of the portion comprising the 3-33 exons of PKD1 gene in mosaic in percentage close to the resolution limits of the used technique (25-30%). The same analysis was confirmed in another laboratory. Conclusion We concluded that the identified large deletion, without establishing the real borders due to MLPA technical restrictions, was present as mosaicism. The variant is not reported, but due to the type of mutation and the clinical picture of the patient, it is to be considered as likely pathogenic. A stepwise genetic approach might be useful in those cases where standard methods do not allow to reach a definitive diagnosis.