Clinical exome sequencing is a powerful tool in the diagnostic flow of monogenic kidney diseases: an Italian experience
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ORIGINAL ARTICLE
Clinical exome sequencing is a powerful tool in the diagnostic flow of monogenic kidney diseases: an Italian experience Tiziana Vaisitti1 · Monica Sorbini1 · Martina Callegari2 · Silvia Kalantari2 · Valeria Bracciamà2 · Francesca Arruga1 · Silvia Bruna Vanzino2 · Sabina Rendine2 · Gabriele Togliatto1 · Daniela Giachino3,4 · Alessandra Pelle3 · Enrico Cocchi5 · Chiara Benvenuta5 · Simone Baldovino4,6 · Cristiana Rollino6 · Roberta Fenoglio6 · Savino Sciascia6 · Michela Tamagnone7 · Corrado Vitale8 · Giovanni Calabrese9 · Luigi Biancone1,10 · Stefania Bussolino11 · Silvana Savoldi11 · Maurizio Borzumati12 · Vincenzo Cantaluppi13 · Fabio Chiappero14 · Silvana Ungari15 · Licia Peruzzi5 · Dario Roccatello4,6 · Antonio Amoroso1,2 · Silvia Deaglio1,2 Received: 28 May 2020 / Accepted: 2 November 2020 © The Author(s) 2020
Abstract Background A considerable minority of patients on waiting lists for kidney transplantation either have no diagnosis (and fall into the subset of undiagnosed cases) because kidney biopsy was not performed or histological findings were non-specific, or do not fall into any well-defined clinical category. Some of these patients might be affected by a previously unrecognised monogenic disease. Methods Through a multidisciplinary cooperative effort, we built an analytical pipeline to identify patients with chronic kidney disease (CKD) with a clinical suspicion of a monogenic condition or without a well-defined diagnosis. Following the stringent phenotypical and clinical characterization required by the flowchart, candidates meeting these criteria were further investigated by clinical exome sequencing followed by in silico analysis of 225 kidney-disease-related genes. Results By using an ad hoc web-based platform, we enrolled 160 patients from 13 different Nephrology and Genetics Units located across the Piedmont region over 15 months. A preliminary “remote” evaluation based on well-defined inclusion criteria allowed us to define eligibility for NGS analysis. Among the 138 recruited patients, 52 (37.7%) were children and 86 (62.3%) were adults. Up to 48% of them had a positive family history for kidney disease. Overall, applying this workflow led to the identification of genetic variants potentially explaining the phenotype in 78 (56.5%) cases. Conclusions These results underline the importance of clinical exome sequencing as a versatile and highly useful, noninvasive tool for genetic diagnosis of kidney diseases. Identifying patients who can benefit from targeted therapies, and improving the management of organ transplantation are further expected applications. Keywords Next-generation sequencing · Chronic kidney failure · Transplantation · Renal monogenic disease
Introduction The importance of genetic contributions in the development chronic kidney disease (CKD) is underlined by several observations: (1) inherited CKD (IKD) represents a high percentage of all CKDs [1–3], (2) the presence of a Electronic supplementary material The online version of this article (https://doi.o
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