Monogenic causes of chronic kidney disease in adults
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Monogenic causes of chronic kidney disease in adults. / Connaughton, Dervla M; Kennedy, Claire; Shril, Shirlee; Mann, Nina; Murray, Susan L; Williams, Patrick A; Conlon, Eoin; Nakayama, Makiko; van der Ven, Amelie T; Ityel, Hadas; Kause, Franziska; Kolvenbach, Caroline M; Dai, Rufeng; Vivante, Asaf; Braun, Daniela A; Schneider, Ronen; Kitzler, Thomas M; Moloney, Brona; Moran, Conor P; Smyth, John S; Kennedy, Alan; Benson, Katherine; Stapleton, Caragh; Denton, Mark; Magee, Colm; O'Seaghdha, Conall M; Plant, William D; Griffin, Matthew D; Awan, Atif; Sweeney, Clodagh; Mane, Shrikant M; Lifton, Richard P; Griffin, Brenda; Leavey, Sean; Casserly, Liam; de Freitas, Declan G; Holian, John; Dorman, Anthony; Doyle, Brendan; Lavin, Peter J; Little, Mark A; Conlon, Peter J; Hildebrandt, Friedhelm.
in: KIDNEY INT, Jahrgang 95, Nr. 4, 04.2019, S. 914-928.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Monogenic causes of chronic kidney disease in adults
AU - Connaughton, Dervla M
AU - Kennedy, Claire
AU - Shril, Shirlee
AU - Mann, Nina
AU - Murray, Susan L
AU - Williams, Patrick A
AU - Conlon, Eoin
AU - Nakayama, Makiko
AU - van der Ven, Amelie T
AU - Ityel, Hadas
AU - Kause, Franziska
AU - Kolvenbach, Caroline M
AU - Dai, Rufeng
AU - Vivante, Asaf
AU - Braun, Daniela A
AU - Schneider, Ronen
AU - Kitzler, Thomas M
AU - Moloney, Brona
AU - Moran, Conor P
AU - Smyth, John S
AU - Kennedy, Alan
AU - Benson, Katherine
AU - Stapleton, Caragh
AU - Denton, Mark
AU - Magee, Colm
AU - O'Seaghdha, Conall M
AU - Plant, William D
AU - Griffin, Matthew D
AU - Awan, Atif
AU - Sweeney, Clodagh
AU - Mane, Shrikant M
AU - Lifton, Richard P
AU - Griffin, Brenda
AU - Leavey, Sean
AU - Casserly, Liam
AU - de Freitas, Declan G
AU - Holian, John
AU - Dorman, Anthony
AU - Doyle, Brendan
AU - Lavin, Peter J
AU - Little, Mark A
AU - Conlon, Peter J
AU - Hildebrandt, Friedhelm
N1 - Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
PY - 2019/4
Y1 - 2019/4
N2 - Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.
AB - Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.
U2 - 10.1016/j.kint.2018.10.031
DO - 10.1016/j.kint.2018.10.031
M3 - SCORING: Journal article
C2 - 30773290
VL - 95
SP - 914
EP - 928
JO - KIDNEY INT
JF - KIDNEY INT
SN - 0085-2538
IS - 4
ER -
