Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients.

TitleWhole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients.
Publication TypeJournal Article
Year of Publication2019
AuthorsMann, N, Braun, DA, Amann, K, Tan, W, Shril, S, Connaughton, DM, Nakayama, M, Schneider, R, Kitzler, TM, van der Ven, AT, Chen, J, Ityel, H, Vivante, A, Majmundar, AJ, Daga, A, Warejko, JK, Lovric, S, Ashraf, S, Jobst-Schwan, T, Widmeier, E, Hugo, H, Mane, SM, Spaneas, L, Somers, MJG, Ferguson, MA, Traum, AZ, Stein, DR, Baum, MA, Daouk, GH, Lifton, RP, Manzi, S, Vakili, K, Kim, HBae, Rodig, NM, Hildebrandt, F
JournalJ Am Soc Nephrol
Date Published2019 02
KeywordsAdolescent, Boston, Child, Child, Preschool, Cohort Studies, Female, Genetic Predisposition to Disease, Genetic Testing, Graft Rejection, Graft Survival, Hospitals, Pediatric, Humans, Kidney Transplantation, Male, Precision Medicine, Prognosis, Renal Insufficiency, Chronic, Retrospective Studies, Risk Assessment, Severity of Illness Index, Survival Analysis, Transplant Recipients, Treatment Outcome, Whole Exome Sequencing

BACKGROUND: Whole-exome sequencing (WES) finds a CKD-related mutation in approximately 20% of patients presenting with CKD before 25 years of age. Although provision of a molecular diagnosis could have important implications for clinical management, evidence is lacking on the diagnostic yield and clinical utility of WES for pediatric renal transplant recipients.

METHODS: To determine the diagnostic yield of WES in pediatric kidney transplant recipients, we recruited 104 patients who had received a transplant at Boston Children's Hospital from 2007 through 2017, performed WES, and analyzed results for likely deleterious variants in approximately 400 genes known to cause CKD.

RESULTS: By WES, we identified a genetic cause of CKD in 34 out of 104 (32.7%) transplant recipients. The likelihood of detecting a molecular genetic diagnosis was highest for patients with urinary stone disease (three out of three individuals), followed by renal cystic ciliopathies (seven out of nine individuals), steroid-resistant nephrotic syndrome (nine out of 21 individuals), congenital anomalies of the kidney and urinary tract (ten out of 55 individuals), and chronic glomerulonephritis (one out of seven individuals). WES also yielded a molecular diagnosis for four out of nine individuals with ESRD of unknown etiology. The WES-related molecular genetic diagnosis had implications for clinical care for five patients.

CONCLUSIONS: Nearly one third of pediatric renal transplant recipients had a genetic cause of their kidney disease identified by WES. Knowledge of this genetic information can help guide management of both transplant patients and potential living related donors.

Alternate JournalJ. Am. Soc. Nephrol.
PubMed ID30655312
PubMed Central IDPMC6362619
Grant ListR01 DK088767 / DK / NIDDK NIH HHS / United States
R01 DK068306 / DK / NIDDK NIH HHS / United States
S10 OD018521 / OD / NIH HHS / United States
UM1 HG008900 / HG / NHGRI NIH HHS / United States
T32 DK007726 / DK / NIDDK NIH HHS / United States
R01 DK076683 / DK / NIDDK NIH HHS / United States
U54 HG006504 / HG / NHGRI NIH HHS / United States