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01-12-2021 | Alport Syndrome | Original Article

Nephroplex: a kidney-focused NGS panel highlights the challenges of PKD1 sequencing and identifies a founder BBS4 mutation

Authors: Miriam Zacchia, Francesca Del Vecchio Blanco, Francesco Trepiccione, Giancarlo Blasio, Annalaura Torella, Andrea Melluso, Giovanna Capolongo, Rosa Maria Pollastro, Giulio Piluso, Valentina Di Iorio, Francesca Simonelli, Davide Viggiano, Alessandra Perna, Vincenzo Nigro, Giovambattista Capasso

Published in: Journal of Nephrology | Issue 6/2021

Abstract

Background

Genetic testing of patients with inherited kidney diseases has emerged as a tool of clinical utility by improving the patients’ diagnosis, prognosis, surveillance and therapy.

Methods

The present study applied a Next Generation Sequencing (NGS)-based panel, named NephroPlex, testing 115 genes causing renal diseases, to 119 individuals, including 107 probands and 12 relatives. Thirty-five (poly)cystic and 72 non (poly)cystic individuals were enrolled. The latter subgroup of patients included Bardet-Biedl syndrome (BBS) patients, as major components.

Results

Disease-causing mutations were identified in 51.5 and 40% of polycystic and non-polycystic individuals, respectively. Autosomal dominant polycystic kidney disease (ADPKD) patients with truncating PKD1 variants showed a trend towards a greater slope of the age-estimated glomerular filtration rate (eGFR) regression line than patients with (i) missense variants, (ii) any PKD2 mutations and (iii) no detected mutations, according to previous findings. The analysis of BBS individuals showed a similar frequency of BBS4,9,10 and 12 mutations. Of note, all BBS4-mutated patients harbored the novel c.332+1G>GTT variant, which was absent in public databases, however, in our internal database, an additional heterozygote carrier was found. All BBS4-mutated individuals originated from the same geographical area encompassing the coastal provinces of Naples.

Discussion

In conclusion, these findings indicate the potential for a genetic panel to provide useful information at both clinical and epidemiological levels.

Graphic abstract

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Title: Nephroplex: a kidney-focused NGS panel highlights the challenges of PKD1 sequencing and identifies a founder BBS4 mutation
Authors: Miriam Zacchia
Francesca Del Vecchio Blanco
Francesco Trepiccione
Giancarlo Blasio
Annalaura Torella
Andrea Melluso
Giovanna Capolongo
Rosa Maria Pollastro
Giulio Piluso
Valentina Di Iorio
Francesca Simonelli
Davide Viggiano
Alessandra Perna
Vincenzo Nigro
Giovambattista Capasso
Publication date: 01-12-2021
Publisher: Springer International Publishing
Keywords: Alport Syndrome
Polycystic Kidney Disease
Metabolic Alkalosis
Alport Syndrome
Published in: Journal of Nephrology / Issue 6/2021
Print ISSN: 1121-8428
Electronic ISSN: 1724-6059
DOI: https://doi.org/10.1007/s40620-021-01048-4

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