Targeted broad-based genetic testing by next-generation sequencing informs diagnosis and facilitates management in patients with kidney diseases. Nephrol Dial Transplant 2021 Jan 25;36(2):295-305
Date
11/19/2019Pubmed ID
31738409Pubmed Central ID
PMC7834596DOI
10.1093/ndt/gfz173Scopus ID
2-s2.0-85100445630 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
BACKGROUND: The clinical diagnosis of genetic renal diseases may be limited by the overlapping spectrum of manifestations between diseases or by the advancement of disease where clues to the original process are absent. The objective of this study was to determine whether genetic testing informs diagnosis and facilitates management of kidney disease patients.
METHODS: We developed a comprehensive genetic testing panel (KidneySeq) to evaluate patients with various phenotypes including cystic diseases, congenital anomalies of the kidney and urinary tract (CAKUT), tubulointerstitial diseases, transport disorders and glomerular diseases. We evaluated this panel in 127 consecutive patients ranging in age from newborns to 81 years who had samples sent in for genetic testing.
RESULTS: The performance of the sequencing pipeline for single-nucleotide variants was validated using CEPH (Centre de'Etude du Polymorphism) controls and for indels using Genome-in-a-Bottle. To test the reliability of the copy number variant (CNV) analysis, positive samples were re-sequenced and analyzed. For patient samples, a multidisciplinary review board interpreted genetic results in the context of clinical data. A genetic diagnosis was made in 54 (43%) patients and ranged from 54% for CAKUT, 53% for ciliopathies/tubulointerstitial diseases, 45% for transport disorders to 33% for glomerulopathies. Pathogenic and likely pathogenic variants included 46% missense, 11% nonsense, 6% splice site variants, 23% insertion-deletions and 14% CNVs. In 13 cases, the genetic result changed the clinical diagnosis.
CONCLUSION: Broad genetic testing should be considered in the evaluation of renal patients as it complements other tests and provides insight into the underlying disease and its management.
Author List
Mansilla MA, Sompallae RR, Nishimura CJ, Kwitek AE, Kimble MJ, Freese ME, Campbell CA, Smith RJ, Thomas CPAuthor
Anne E. Kwitek PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Aged, 80 and over
Biomarkers
Child
Child, Preschool
DNA Copy Number Variations
Female
Genetic Testing
High-Throughput Nucleotide Sequencing
Humans
Infant
Infant, Newborn
Kidney Diseases
Male
Middle Aged
Mutation
Phenotype
Reproducibility of Results
Young Adult
