Diagnostic Utility of Exome Sequencing for Kidney Disease
| Autor: | Hila Milo-Rasouly, Sophia R. Cameron-Christie, Vimla Aggarwal, Carolina Haefliger, Byum Hee Kil, Adam Platt, Brett Copeland, Andrew S. Bomback, Wan Yee Lam, Natalie S Uy, Simone Sanna-Cherchi, Junying Zhang, Rachel Reingold, Zhong Ren, Stacy Piva, Adele Mitrotti, David J. Cohen, Debanjana Chatterjee, Ruth March, Emily E. Groopman, Maddalena Marasa, Drew Bradbury, Sumit Mohan, Michael DiVecchia, David Goldstein, Shumyle Alam, Colin D. Malone, Jordan G. Nestor, Jan Fleckner, Chunhua Weng, Gerald B. Appel, Yifu Li, Priya Krithivasan, Russell J. Crew, Neha Dagaonkar, Olivia Balderes, Karla Mehl, David Fasel, Holly J. Snyder, Maya K. Rao, Joshua Bridgers, Geoffrey K. Dube, Krzysztof Kiryluk, Pietro A. Canetta, Bengt Fellström, Ali G. Gharavi, Jai Radhakrishnan, Wooin Ahn, Caroline Mebane, Slavé Petrovski, Xueru Mu, Sitharthan Kamalakaran |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Nephrology medicine.medical_specialty Diagnostic methods Computational biology 030204 cardiovascular system & hematology Article Cohort Studies Young Adult 03 medical and health sciences 0302 clinical medicine Internal medicine Exome Sequencing Humans Medicine Genetic Predisposition to Disease Exome Genetic Testing 030212 general & internal medicine Renal Insufficiency Chronic Exome sequencing Aged business.industry Extramural Genetic Variation Sequence Analysis DNA General Medicine Middle Aged medicine.disease Mutation Medical genetics business Glomerular Filtration Rate Kidney disease |
| Zdroj: | New England Journal of Medicine. 380:142-151 |
| ISSN: | 1533-4406 0028-4793 |
| Popis: | 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. (Funded by the National Institutes of Health and others.) |
| Databáze: | OpenAIRE |
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