Monogenic causes of chronic kidney disease in adults.
Adolescent
Adult
Age of Onset
Aged
Aged, 80 and over
Cohort Studies
Exome
/ genetics
Female
Genetic Predisposition to Disease
Genetic Testing
/ methods
Humans
Ireland
Kidney
Male
Medical History Taking
Middle Aged
Mutation
Pedigree
Precision Medicine
Renal Insufficiency, Chronic
/ diagnosis
Exome Sequencing
Young Adult
chronic kidney disease
genetic kidney disease
whole exome sequencing
Journal
Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
29
05
2018
revised:
10
10
2018
accepted:
19
10
2018
pubmed:
19
2
2019
medline:
15
2
2020
entrez:
19
2
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30773290
pii: S0085-2538(18)30839-1
doi: 10.1016/j.kint.2018.10.031
pmc: PMC6431580
mid: NIHMS1516136
pii:
doi:
Types de publication
Evaluation Study
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
914-928Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK088767
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK079310
Pays : United States
Organisme : NIH HHS
ID : S10 OD018521
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK076683
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009172
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG006504
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK068306
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007726
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
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