Kidney Week

Abstract: PUB291

Mosaicism in a Patient with ADPKD: A Case Report

Session Information

• Publication Only

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic

Authors

• Marzano, Nenzi, International Renal Research Institute (IRRIV) Foundation, Vicenza, Italy

Nenzi Marzano

• Caprara, Carlotta, International Renal Research Institute (IRRIV) Foundation, Vicenza, Italy

Carlotta Caprara

• Reis, Thiago A., Laboratory of Molecular Pharmacology, University of Brasilia, Brasilia, Brazil

Thiago A. Reis, MD

• Pomare' Montin, Diego, International Renal Research Institute (IRRIV) Foundation, Vicenza, Italy

Diego Pomare' Montin

• Pretto, Sofia Maria, International Renal Research Institute (IRRIV) Foundation, Vicenza, Italy

Sofia Maria Pretto

• Rigato, Matteo, International Renal Research Institute (IRRIV) Foundation, Vicenza, Italy

Matteo Rigato

• Gastaldon, Fiorella, UOC Nefrology, ULSS 8 Berica, San Bortolo Hospital, Vicenza, Italy

Fiorella Gastaldon

• Ronco, Claudio, International Renal Research Institute (IRRIV) Foundation, Vicenza, Italy

Claudio Ronco, MD

• Zanella, Monica, International Renal Research Institute (IRRIV) Foundation, Vicenza, Italy

Monica Zanella, MD

• Corradi, Valentina, International Renal Research Institute (IRRIV) Foundation, Vicenza, Italy

Valentina Corradi

Introduction

Autosomal Dominant Polycystic Kidney Disease (ADPKD), considered the most frequent genetic renal disease, is characterized by renal involvement with progressive bilateral development of renal cysts and volumetric increase of kidneys, causing loss of renal function leading to chronic kidney disease (CKD). ADPKD has a complex inheritance and a wide phenotypic variability. In some cases, it is necessary to perform genetic testing to achieve a definitive diagnosis. The occurrence of mosaicism, described by a few cell populations with different genomes, may modify the presentation of the disease, modulate its clinical course, and better define an ADPKD population.

Case Description

The case describes a 47-year-old woman presenting typical ultrasound and computed tomography features of ADPKD. She had CKD stage 3b and hypertension. There was no family history of ADPKD, prompting an investigation with a genetic test. Next Generation Sequencing (NGS, nephropathies solution gene panel) did not detect the presence of any genomic variants. The CGH array negative result confirmed the NGS analysis. Multiple Ligation-dependent Probe Amplification (MLPA) for the investigation of large rearrangement of PKD1 and PKD2 genes showed a large deletion (PKD1 gene, exons 3-33) present in heterozygosis with a percentage of cells close to the resolution limits of the used technique (<25-30%). The MLPA analysis was repeated after a revision of the used kit, making it possible to better define the border of the deletion. The new result showed a deletion in heterozygosis of exons 2-34 in PKD1: NC_000016.10: g. (2136179_2119520) (2097184_2094247) del, chr16:2094247: 2136179: del.

Discussion

We concluded that the mutation is present as mosaic, a genetic condition of difficult detection since there are no election methods for its molecular identification. The deletion present in mosaic may have contributed to the attenuated reduction in kidney function compared to PKD1 protein-truncating mutations. The variant is not reported, but due to the type of mutation and the patient’s clinical picture, it is to be considered as likely pathogenic. This case highlights how a stepwise genetic approach might be useful when standard methods do not allow to reach a definitive diagnosis.