Typical Clinical Presentation of an Autosomal Dominant Polycystic Kidney Disease Patient with an Atypical Genetic Pattern

<b>Background</b>: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is mainly characterized by renal involvement with progressive bilateral development of renal cysts and volumetric increase in the kidneys, causing a loss of renal function, chronic kidney disease (CKD), and kidney failure. The occurrence of mosaicism may modulate the clinical course of the disease. Mosaicism is characterized by a few cell populations with different genomes. In these special cases, a genetic diagnosis could be challenging. <b>Methods</b>: Herein, we describe the case of a 47-year-old woman presenting with typical ultrasound and computed tomography features of ADPKD. She had stage 3b CKD and hypertension. There was no family history of ADPKD, prompting an investigation with a genetic test. Target next-generation sequencing (NGS) did not detect the presence of any genomic variants. Therefore, we carried out second-level genetic analysis to investigate the presence of a large rearrangement through a multiple ligation-dependent probe amplification (MLPA) analysis of PKD1 and PKD2 genes. <b>Results</b>: MLPA showed a large deletion (portion including exons 2-34 of PKD1) present in the heterozygosis with a percentage of cells close to the resolution limits of the technique used (<25-30%). We concluded that the large deletion identified was mosaicism. This variant is not reported in major ADPKD databases, but due to the type of mutation and the patient's clinical picture, it should be considered as likely pathogenic. <b>Conclusions</b>: A stepwise genetic approach might be useful in those cases where standard methods do not allow one to reach a definitive diagnosis.