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Genetic Testing for Steroid-Resistant-Nephrotic Syndrome in an Outbred Population.

Publication ,  Journal Article
Varner, JD; Chryst-Stangl, M; Esezobor, CI; Solarin, A; Wu, G; Lane, B; Hall, G; Abeyagunawardena, A; Matory, A; Hunley, TE; Lin, JJ ...
Published in: Front Pediatr
2018

Background: Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage kidney disease in children and young adults. Despite advances in genomic science that have led to the discovery of >50 monogenic causes of SRNS, there are no clear guidelines for genetic testing in clinical practice. Methods: Using high throughput sequencing, we evaluated 492 individuals from 181 families for mutations in 40 known SRNS genes. Causative mutations were defined as missense, truncating, and obligatory splice site variants with a minor allele frequency <1% in controls. Non-synonymous variants were considered pathogenic if determined to be deleterious by at least two in silico models. We further evaluated for differences in age at disease onset, family history of SRNS or chronic kidney disease, race, sex, renal biopsy findings, and extra-renal manifestations in subgroups with and without disease causing variants. Results: We identified causative variants in 40 of 181 families (22.1%) with SRNS. Variants in INF2, COL4A3, and WT1 were the most common, accounting for over half of all causative variants. Causative variants were identified in 34 of 86 families (39.5%) with familial disease and 6 of 95 individuals (6.3%) with sporadic disease (χ2 p < 0.00001). Family history was the only significant clinical predictor of genetic SRNS. Conclusion: We identified causative mutations in almost 40% of all families with hereditary SRNS and 6% of individuals with sporadic disease, making family history the single most important clinical predictors of monogenic SRNS. We recommend genetic testing in all patients with SRNS and a positive family history, but only selective testing in those with sporadic disease.

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Published In

Front Pediatr

DOI

ISSN

2296-2360

Publication Date

2018

Volume

6

Start / End Page

307

Location

Switzerland

Related Subject Headings

  • 3213 Paediatrics
  • 1199 Other Medical and Health Sciences
  • 1114 Paediatrics and Reproductive Medicine
 

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Chicago
ICMJE
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Varner, J. D., Chryst-Stangl, M., Esezobor, C. I., Solarin, A., Wu, G., Lane, B., … Gbadegesin, R. (2018). Genetic Testing for Steroid-Resistant-Nephrotic Syndrome in an Outbred Population. Front Pediatr, 6, 307. https://doi.org/10.3389/fped.2018.00307
Varner, Jennifer D., Megan Chryst-Stangl, Christopher Imokhuede Esezobor, Adaobi Solarin, Guanghong Wu, Brandon Lane, Gentzon Hall, et al. “Genetic Testing for Steroid-Resistant-Nephrotic Syndrome in an Outbred Population.Front Pediatr 6 (2018): 307. https://doi.org/10.3389/fped.2018.00307.
Varner JD, Chryst-Stangl M, Esezobor CI, Solarin A, Wu G, Lane B, et al. Genetic Testing for Steroid-Resistant-Nephrotic Syndrome in an Outbred Population. Front Pediatr. 2018;6:307.
Varner, Jennifer D., et al. “Genetic Testing for Steroid-Resistant-Nephrotic Syndrome in an Outbred Population.Front Pediatr, vol. 6, 2018, p. 307. Pubmed, doi:10.3389/fped.2018.00307.
Varner JD, Chryst-Stangl M, Esezobor CI, Solarin A, Wu G, Lane B, Hall G, Abeyagunawardena A, Matory A, Hunley TE, Lin JJ, Howell D, Gbadegesin R. Genetic Testing for Steroid-Resistant-Nephrotic Syndrome in an Outbred Population. Front Pediatr. 2018;6:307.

Published In

Front Pediatr

DOI

ISSN

2296-2360

Publication Date

2018

Volume

6

Start / End Page

307

Location

Switzerland

Related Subject Headings

  • 3213 Paediatrics
  • 1199 Other Medical and Health Sciences
  • 1114 Paediatrics and Reproductive Medicine