Exome-First Strategy in Adult Patients With CKD: A Cohort Study
Alice Doreille, Yannis Lombardi, Marine Dancer, Radoslava Saraeva Lamri, Quentin Testard, Xavier Vanhoye, Anne-Sophie Lèbre, Hugo García, Cédric Rafat, Nacéra Ouali, Yosu Luque, Hassan Izzedine, Emmanuel Estève, Alexandre Cez, Camille Petit-Hoang, Hélène François, A. Marchal, Emmanuel Letavernier, Véronique Frémeaux‐Bacchi, Jean‐Jacques Boffa, Éric Rondeau, Laure Raymond, Laurent Mesnard
Abstract
Introduction: Exome sequencing (ES) has widened the field of nephrogenomics in adult nephrology. In addition to reporting the diagnostic yield of ES in an adult cohort study, we investigated the clinical implications of molecular diagnosis and developed a clinical score to predict the probability of obtaining positive result. Methods: From September 2018 we have used ES to prospectively perform a first-tier liberal exploration of adult nephropathies of unknown origin and/or when a genetic kidney disease was clinically suggested. We also analyzed copy number variant using the same assay. Results: = 125/127) of the patients, the genetic information was reported to have major clinical implications. We developed a 4-value clinical score to predict the probability of obtaining a molecular diagnosis (area under the receiver operating characteristics curve [AUC] 0.726 [95% confidence interval: 0.670-0.782]) (available at http://allogenomics.com/score). Conclusion: This study reinforces the role of ES as a first-tier exploration for adult chronic kidney disease patients in whom phenotypes are often poor and atypical. Although external validation is required, our clinical score could be a useful tool for the implementation of nephrogenomics in adults.