Targeted broad-based genetic testing by next-generation sequencing informs diagnosis and facilitates management in patients with kidney diseases

M Adela Mansilla; Ramakrishna Sompallae; Carla Nishimura; Anne Kwitek; Mycah Kimble; Margaret Freese; Colleen Campbell; Richard Smith; Christie Thomas

doi:10.1093/ndt/gfz173

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Targeted broad-based genetic testing by next-generation sequencing informs diagnosis and facilitates management in patients with kidney diseases

Journal article

Open access

Peer reviewed

Targeted broad-based genetic testing by next-generation sequencing informs diagnosis and facilitates management in patients with kidney diseases

M Adela Mansilla, Ramakrishna Sompallae, Carla Nishimura, Anne Kwitek, Mycah Kimble, Margaret Freese, Colleen Campbell, Richard Smith and Christie Thomas

Nephrology Dialysis Transplantation, Vol.36(2), pp.295-305

2021

DOI: 10.1093/ndt/gfz173

PMCID: PMC7834596

PMID: 31738409

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Abstract

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.

Genetics

Kidney Diseases

Details

Title: Subtitle: Targeted broad-based genetic testing by next-generation sequencing informs diagnosis and facilitates management in patients with kidney diseases
Creators: M Adela Mansilla
Ramakrishna Sompallae
Carla Nishimura
Anne Kwitek
Mycah Kimble
Margaret Freese
Colleen Campbell
Richard Smith
Christie Thomas
Resource Type: Journal article
Publication Details: Nephrology Dialysis Transplantation, Vol.36(2), pp.295-305
DOI: 10.1093/ndt/gfz173
PMID: 31738409
PMCID: PMC7834596
NLM abbreviation: Nephrol Dial Transplant
ISSN: 0931-0509
eISSN: 1460-2385
Publisher: Oxford University Press
Language: English
Date published: 2021
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Obstetrics and Gynecology; Otolaryngology; Internal Medicine; Iowa Institute of Human Genetics
Record Identifier: 9983986081402771

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