Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients
Standard
Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients. / Mann, Nina; Braun, Daniela A; Amann, Kassaundra; Tan, Weizhen; Shril, Shirlee; Connaughton, Dervla M; Nakayama, Makiko; Schneider, Ronen; Kitzler, Thomas M; van der Ven, Amelie T; Chen, Jing; Ityel, Hadas; Vivante, Asaf; Majmundar, Amar J; Daga, Ankana; Warejko, Jillian K; Lovric, Svjetlana; Ashraf, Shazia; Jobst-Schwan, Tilman; Widmeier, Eugen; Hugo, Hannah; Mane, Shrikant M; Spaneas, Leslie; Somers, Michael J G; Ferguson, Michael A; Traum, Avram Z; Stein, Deborah R; Baum, Michelle A; Daouk, Ghaleb H; Lifton, Richard P; Manzi, Shannon; Vakili, Khashayar; Kim, Heung Bae; Rodig, Nancy M; Hildebrandt, Friedhelm.
in: J AM SOC NEPHROL, Jahrgang 30, Nr. 2, 02.2019, S. 201-215.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients
AU - Mann, Nina
AU - Braun, Daniela A
AU - Amann, Kassaundra
AU - Tan, Weizhen
AU - Shril, Shirlee
AU - Connaughton, Dervla M
AU - Nakayama, Makiko
AU - Schneider, Ronen
AU - Kitzler, Thomas M
AU - van der Ven, Amelie T
AU - Chen, Jing
AU - Ityel, Hadas
AU - Vivante, Asaf
AU - Majmundar, Amar J
AU - Daga, Ankana
AU - Warejko, Jillian K
AU - Lovric, Svjetlana
AU - Ashraf, Shazia
AU - Jobst-Schwan, Tilman
AU - Widmeier, Eugen
AU - Hugo, Hannah
AU - Mane, Shrikant M
AU - Spaneas, Leslie
AU - Somers, Michael J G
AU - Ferguson, Michael A
AU - Traum, Avram Z
AU - Stein, Deborah R
AU - Baum, Michelle A
AU - Daouk, Ghaleb H
AU - Lifton, Richard P
AU - Manzi, Shannon
AU - Vakili, Khashayar
AU - Kim, Heung Bae
AU - Rodig, Nancy M
AU - Hildebrandt, Friedhelm
N1 - Copyright © 2019 by the American Society of Nephrology.
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - Adolescent
KW - Boston
KW - Child
KW - Child, Preschool
KW - Cohort Studies
KW - Female
KW - Genetic Predisposition to Disease/epidemiology
KW - Genetic Testing/methods
KW - Graft Rejection
KW - Graft Survival
KW - Hospitals, Pediatric
KW - Humans
KW - Kidney Transplantation/adverse effects
KW - Male
KW - Precision Medicine/methods
KW - Prognosis
KW - Renal Insufficiency, Chronic/genetics
KW - Retrospective Studies
KW - Risk Assessment
KW - Severity of Illness Index
KW - Survival Analysis
KW - Transplant Recipients/statistics & numerical data
KW - Treatment Outcome
KW - Whole Exome Sequencing/methods
U2 - 10.1681/ASN.2018060575
DO - 10.1681/ASN.2018060575
M3 - SCORING: Journal article
C2 - 30655312
VL - 30
SP - 201
EP - 215
JO - J AM SOC NEPHROL
JF - J AM SOC NEPHROL
SN - 1046-6673
IS - 2
ER -
