Clinical exome sequencing is a powerful tool in the diagnostic flow of monogenic kidney diseases: an Italian experience.

Autor: Vaisitti T; Department of Medical Sciences, University of Turin, via Santena 19, 10126, Turin, Italy., Sorbini M; Department of Medical Sciences, University of Turin, via Santena 19, 10126, Turin, Italy., Callegari M; Immunogenetics and Transplant Biology Service, Città della Salute e della Scienza University Hospital, Turin, Italy., Kalantari S; Immunogenetics and Transplant Biology Service, Città della Salute e della Scienza University Hospital, Turin, Italy., Bracciamà V; Immunogenetics and Transplant Biology Service, Città della Salute e della Scienza University Hospital, Turin, Italy., Arruga F; Department of Medical Sciences, University of Turin, via Santena 19, 10126, Turin, Italy., Vanzino SB; Immunogenetics and Transplant Biology Service, Città della Salute e della Scienza University Hospital, Turin, Italy., Rendine S; Immunogenetics and Transplant Biology Service, Città della Salute e della Scienza University Hospital, Turin, Italy., Togliatto G; Department of Medical Sciences, University of Turin, via Santena 19, 10126, Turin, Italy., Giachino D; Service of Genetic Counseling, San Luigi Gonzaga University Hospital, Orbassano, Turin, Italy.; Department of Clinical and Biological Sciences, University of Turin, Turin, Italy., Pelle A; Service of Genetic Counseling, San Luigi Gonzaga University Hospital, Orbassano, Turin, Italy., Cocchi E; Pediatric Nephrology Dialysis and Transplantation Unit, Città della Salute e della Scienza University Hospital, Turin, Italy., Benvenuta C; Pediatric Nephrology Dialysis and Transplantation Unit, Città della Salute e della Scienza University Hospital, Turin, Italy., Baldovino S; Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.; Nephrology and Dialysis Unit (ERKnet Member)-CMID, Center of Research of Immunopathology and Rare Diseases, San Giovanni Bosco Hospital, Turin, Italy., Rollino C; Nephrology and Dialysis Unit (ERKnet Member)-CMID, Center of Research of Immunopathology and Rare Diseases, San Giovanni Bosco Hospital, Turin, Italy., Fenoglio R; Nephrology and Dialysis Unit (ERKnet Member)-CMID, Center of Research of Immunopathology and Rare Diseases, San Giovanni Bosco Hospital, Turin, Italy., Sciascia S; Nephrology and Dialysis Unit (ERKnet Member)-CMID, Center of Research of Immunopathology and Rare Diseases, San Giovanni Bosco Hospital, Turin, Italy., Tamagnone M; Nephrology and Dialysis Unit ASL CN1, Cuneo, Italy., Vitale C; Nephrology and Dialysis Unit, Ordine Mauriziano di Torino, Turin, Italy., Calabrese G; Nephrology and Dialysis Unit ASL AL, Alessandria, Italy., Biancone L; Department of Medical Sciences, University of Turin, via Santena 19, 10126, Turin, Italy.; Renal Transplantation Unit 'A. Vercellone,' Division of Nephrology Dialysis and Transplantation, Città della Salute e della Scienza University Hospital, Turin, Italy., Bussolino S; Nephrology and Dialysis Unit ASL TO4, Turin, Italy., Savoldi S; Nephrology and Dialysis Unit ASL TO4, Turin, Italy., Borzumati M; Nephrology and Dialysis Unit of Verbania ASL VCO, Verbano Cusio Ossola, Verbania, Italy., Cantaluppi V; Nephrology and Kidney Transplantation Unit, Maggiore Della Carità University Hospital, Novara, Italy., Chiappero F; Nephrology and Dialysis Unit ASL TO3, Turin, Italy., Ungari S; Struttura Semplice Genetics and Molecular Biology, ASL CN1, Cuneo, Italy., Peruzzi L; Pediatric Nephrology Dialysis and Transplantation Unit, Città della Salute e della Scienza University Hospital, Turin, Italy., Roccatello D; Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.; Nephrology and Dialysis Unit (ERKnet Member)-CMID, Center of Research of Immunopathology and Rare Diseases, San Giovanni Bosco Hospital, Turin, Italy., Amoroso A; Department of Medical Sciences, University of Turin, via Santena 19, 10126, Turin, Italy. antonio.amoroso@unito.it.; Immunogenetics and Transplant Biology Service, Città della Salute e della Scienza University Hospital, Turin, Italy. antonio.amoroso@unito.it., Deaglio S; Department of Medical Sciences, University of Turin, via Santena 19, 10126, Turin, Italy.; Immunogenetics and Transplant Biology Service, Città della Salute e della Scienza University Hospital, Turin, Italy.
Jazyk: angličtina
Zdroj: Journal of nephrology [J Nephrol] 2021 Oct; Vol. 34 (5), pp. 1767-1781. Date of Electronic Publication: 2020 Nov 23.
DOI: 10.1007/s40620-020-00898-8
Abstrakt: 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, non-invasive 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.
(© 2020. The Author(s).)
Databáze: MEDLINE
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