Diagnostic Utility of exome sequencing for kidney disease

Emily E. Groopman, Maddalena Marasa, Sophia Cameron-Christie, Slavé Petrovski, Vimla S. Aggarwal, Hila Milo-Rasouly, Yifu Li, Junying Zhang, Jordan Nestor, Priya Krithivasan, Wan Yee Lam, Adele Mitrotti, Stacy Piva, Byum H. Kil, Debanjana Chatterjee, Rachel Reingold, Drew Bradbury, Michael DiVecchia, Holly Snyder, Xueru MuKarla Mehl, Olivia Balderes, David A. Fasel, Chunhua Weng, Jai Radhakrishnan, Pietro Canetta, Gerald B. Appel, Andrew S. Bomback, Wooin Ahn, Natalie S. Uy, Shumyle Alam, David J. Cohen, Russell J. Crew, Geoffrey K. Dube, Maya K. Rao, Sitharthan Kamalakaran, Brett Copeland, Zhong Ren, Joshua Bridgers, Colin D. Malone, Caroline M. Mebane, Neha Dagaonkar, Bengt C. Fellström, Carolina Haefliger, Sumit Mohan, Simone Sanna-Cherchi, Krzysztof Kiryluk, Jan Fleckner, Ruth March, Adam Platt, David B. Goldstein, Ali G. Gharavi

Research output: Contribution to journalArticlepeer-review

417 Scopus citations


BACKGROUND Exome sequencing is emerging as a first-line diagnostic method in some clinical disciplines, but its usefulness has yet to be examined for most constitutional disorders in adults, including chronic kidney disease, which affects more than 1 in 10 persons globally. METHODS We conducted exome sequencing and diagnostic analysis in two cohorts totaling 3315 patients with chronic kidney disease. We assessed the diagnostic yield and, among the patients for whom detailed clinical data were available, the clinical implications of diagnostic and other medically relevant findings. RESULTS In all, 3037 patients (91.6%) were over 21 years of age, and 1179 (35.6%) were of self-identified non-European ancestry. We detected diagnostic variants in 307 of the 3315 patients (9.3%), encompassing 66 different monogenic disorders. Of the disorders detected, 39 (59%) were found in only a single patient. Diagnostic variants were detected across all clinically defined categories, including congenital or cystic renal disease (127 of 531 patients [23.9%]) and nephropathy of unknown origin (48 of 281 patients [17.1%]). Of the 2187 patients assessed, 34 (1.6%) had genetic findings for medically actionable disorders that, although unrelated to their nephropathy, would also lead to subspecialty referral and inform renal management. CONCLUSIONS Exome sequencing in a combined cohort of more than 3000 patients with chronic kidney disease yielded a genetic diagnosis in just under 10% of cases.

Original languageEnglish
Pages (from-to)142-151
Number of pages10
JournalNew England Journal of Medicine
Issue number2
StatePublished - 10 Jan 2019
Externally publishedYes


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