Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Article Collections
    • JASN Podcasts
    • Archives
    • Saved Searches
    • ASN Meeting Abstracts
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Subscriptions
  • More
    • About JASN
    • Alerts
    • Advertising
    • Editorial Fellowship Team
    • Feedback
    • Reprints
    • Impact Factor
  • ASN Kidney News
  • Other
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Article Collections
    • JASN Podcasts
    • Archives
    • Saved Searches
    • ASN Meeting Abstracts
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Subscriptions
  • More
    • About JASN
    • Alerts
    • Advertising
    • Editorial Fellowship Team
    • Feedback
    • Reprints
    • Impact Factor
  • ASN Kidney News
  • Follow JASN on Twitter
  • Visit ASN on Facebook
  • Follow JASN on RSS
  • Community Forum
Basic Research
You have accessRestricted Access

A Single-Gene Cause in 29.5% of Cases of Steroid-Resistant Nephrotic Syndrome

Carolin E. Sadowski, Svjetlana Lovric, Shazia Ashraf, Werner L. Pabst, Heon Yung Gee, Stefan Kohl, Susanne Engelmann, Virginia Vega-Warner, Humphrey Fang, Jan Halbritter, Michael J. Somers, Weizhen Tan, Shirlee Shril, Inès Fessi, Richard P. Lifton, Detlef Bockenhauer, Sherif El-Desoky, Jameela A. Kari, Martin Zenker, Markus J. Kemper, Dominik Mueller, Hanan M. Fathy, Neveen A. Soliman, the SRNS Study Group and Friedhelm Hildebrandt
JASN June 2015, 26 (6) 1279-1289; DOI: https://doi.org/10.1681/ASN.2014050489
Carolin E. Sadowski
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Svjetlana Lovric
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shazia Ashraf
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Werner L. Pabst
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heon Yung Gee
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stefan Kohl
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susanne Engelmann
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Virginia Vega-Warner
†Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Humphrey Fang
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jan Halbritter
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael J. Somers
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Weizhen Tan
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shirlee Shril
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Inès Fessi
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard P. Lifton
‡Department of Genetics and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Detlef Bockenhauer
§Institute of Child Health, University College London, London, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sherif El-Desoky
‖Pediatric Nephrology Unit, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jameela A. Kari
‖Pediatric Nephrology Unit, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martin Zenker
¶Department of Human Genetics, Otto von Guericke University, Magdeburg, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Markus J. Kemper
**Department of Pediatrics, University Hospital Hamburg-Eppendorf, Hamburg, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dominik Mueller
††Department of Pediatric Nephrology, Medical Faculty of the Charité, Berlin, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hanan M. Fathy
‡‡The Pediatric Nephrology Unit, Alexandria University, Alexandria, Egypt;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Neveen A. Soliman
§§Department of Pediatrics, Center of Pediatric Nephrology & Transplantation, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt;
‖‖Egyptian Group for Orphan Renal Diseases, Cairo, Egypt; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Friedhelm Hildebrandt
*Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts;
¶¶Howard Hughes Medical Institute, Chevy Chase, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data Supps
  • Info & Metrics
  • View PDF
Loading

Abstract

Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of ESRD in the first two decades of life. Effective treatment is lacking. First insights into disease mechanisms came from identification of single-gene causes of SRNS. However, the frequency of single-gene causation and its age distribution in large cohorts are unknown. We performed exon sequencing of NPHS2 and WT1 for 1783 unrelated, international families with SRNS. We then examined all patients by microfluidic multiplex PCR and next-generation sequencing for all 27 genes known to cause SRNS if mutated. We detected a single-gene cause in 29.5% (526 of 1783) of families with SRNS that manifested before 25 years of age. The fraction of families in whom a single-gene cause was identified inversely correlated with age of onset. Within clinically relevant age groups, the fraction of families with detection of the single-gene cause was as follows: onset in the first 3 months of life (69.4%), between 4 and 12 months old (49.7%), between 1 and 6 years old (25.3%), between 7 and 12 years old (17.8%), and between 13 and 18 years old (10.8%). For PLCE1, specific mutations correlated with age of onset. Notably, 1% of individuals carried mutations in genes that function within the coenzyme Q10 biosynthesis pathway, suggesting that SRNS may be treatable in these individuals. Our study results should facilitate molecular genetic diagnostics of SRNS, etiologic classification for therapeutic studies, generation of genotype-phenotype correlations, and the identification of individuals in whom a targeted treatment for SRNS may be available.

  • SRNS
  • steroid-resistant nephrotic syndrome
  • nephrosis
  • kidney failure
  • genetic disease
  • FSGS
  • Copyright © 2015 by the American Society of Nephrology
View Full Text
PreviousNext
Back to top

In this issue

Journal of the American Society of Nephrology: 26 (6)
Journal of the American Society of Nephrology
Vol. 26, Issue 6
June 2015
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in JASN.
Enter multiple addresses on separate lines or separate them with commas.
A Single-Gene Cause in 29.5% of Cases of Steroid-Resistant Nephrotic Syndrome
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
A Single-Gene Cause in 29.5% of Cases of Steroid-Resistant Nephrotic Syndrome
Carolin E. Sadowski, Svjetlana Lovric, Shazia Ashraf, Werner L. Pabst, Heon Yung Gee, Stefan Kohl, Susanne Engelmann, Virginia Vega-Warner, Humphrey Fang, Jan Halbritter, Michael J. Somers, Weizhen Tan, Shirlee Shril, Inès Fessi, Richard P. Lifton, Detlef Bockenhauer, Sherif El-Desoky, Jameela A. Kari, Martin Zenker, Markus J. Kemper, Dominik Mueller, Hanan M. Fathy, Neveen A. Soliman, the SRNS Study Group, Friedhelm Hildebrandt
JASN Jun 2015, 26 (6) 1279-1289; DOI: 10.1681/ASN.2014050489

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
A Single-Gene Cause in 29.5% of Cases of Steroid-Resistant Nephrotic Syndrome
Carolin E. Sadowski, Svjetlana Lovric, Shazia Ashraf, Werner L. Pabst, Heon Yung Gee, Stefan Kohl, Susanne Engelmann, Virginia Vega-Warner, Humphrey Fang, Jan Halbritter, Michael J. Somers, Weizhen Tan, Shirlee Shril, Inès Fessi, Richard P. Lifton, Detlef Bockenhauer, Sherif El-Desoky, Jameela A. Kari, Martin Zenker, Markus J. Kemper, Dominik Mueller, Hanan M. Fathy, Neveen A. Soliman, the SRNS Study Group, Friedhelm Hildebrandt
JASN Jun 2015, 26 (6) 1279-1289; DOI: 10.1681/ASN.2014050489
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion
    • Concise Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data Supps
  • Info & Metrics
  • View PDF

More in this TOC Section

  • Impairment of Proteasome Function in Podocytes Leads to CKD
  • Mutations in PRDM15 Are a Novel Cause of Galloway-Mowat Syndrome
  • SRGAP1 Controls Small Rho GTPases To Regulate Podocyte Foot Process Maintenance
Show more Basic Research

Cited By...

  • Recessive NOS1AP variants impair actin remodeling and cause glomerulopathy in humans and mice
  • Clinical utility of genetic and genomic testing in the precision diagnosis and management of pediatric patients with kidney and urinary tract diseases
  • Genetic Disorders of the Glomerular Filtration Barrier
  • Clinical Genetic Screening in Adult Patients with Kidney Disease
  • The Use of Genomics to Drive Kidney Disease Drug Discovery and Development
  • Beyond Panel-Based Testing: Exome Analysis Increases Sensitivity for Diagnosis of Genetic Kidney Disease
  • Individualizing Treatment of Steroid-Resistant Nephrotic Syndrome: Registries to the Fore
  • "Its In Your Genes": Exome Sequencing Enables Precision Diagnostics in Proteinuric Kidney Diseases
  • Reverse Phenotyping after Whole-Exome Sequencing in Steroid-Resistant Nephrotic Syndrome
  • Contributions of Rare Gene Variants to Familial and Sporadic FSGS
  • Comprehensive evaluation of a prospective Australian patient cohort with suspected genetic kidney disease undergoing clinical genomic testing: a study protocol
  • A Bigenic mouse model of FSGS reveals perturbed pathways in podocytes, mesangial cells and endothelial cells
  • Molecular genetic analysis of Steroid Resistant Nephrotic Syndrome: Detection of a novel mutation
  • Evaluating Mendelian nephrotic syndrome genes for evidence of risk alleles or oligogenicity that explain heritability
  • Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients
  • Whole-Exome Sequencing Identifies Causative Mutations in Families with Congenital Anomalies of the Kidney and Urinary Tract
  • Strong Association of the HLA-DR/DQ Locus with Childhood Steroid-Sensitive Nephrotic Syndrome in the Japanese Population
  • Clinical syndromes associated with Coenzyme Q10 deficiency
  • Whole Exome Sequencing Reveals a Monogenic Cause of Disease in {approx}43% of 35 Families With Midaortic Syndrome
  • Endoplasmic reticulum-retained podocin mutants are massively degraded by the proteasome
  • Need to Reclassify Etiologies of ESRD on the CMS 2728 Medical Evidence Report
  • Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach
  • Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome
  • Clinical genetic testing using a custom-designed steroid-resistant nephrotic syndrome gene panel: analysis and recommendations
  • Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children
  • New Insights into Podocyte Biology in Glomerular Health and Disease
  • MAGI2 Mutations Cause Congenital Nephrotic Syndrome
  • Modeling Monogenic Human Nephrotic Syndrome in the Drosophila Garland Cell Nephrocyte
  • Focal Segmental Glomerulosclerosis
  • PLC{varepsilon}1 regulates SDF-1{alpha}-induced lymphocyte adhesion and migration to sites of inflammation
  • Minimal Change Disease
  • Recurrent FSGS Postkidney Transplant: Moving the Needle Forward
  • Using Population Genetics to Interrogate the Monogenic Nephrotic Syndrome Diagnosis in a Case Cohort
  • Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid-Resistant Nephrotic Syndrome
  • Google Scholar

Similar Articles

Related Articles

  • PubMed
  • Google Scholar

Keywords

  • SRNS
  • steroid-resistant nephrotic syndrome
  • nephrosis
  • kidney failure
  • genetic disease
  • FSGS

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Annual Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Author Resources
  • Editorial Fellowship Program
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • JASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About JASN
  • JASN Email Alerts
  • JASN Key Impact Information
  • JASN Podcasts
  • JASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe

© 2021 American Society of Nephrology

Print ISSN - 1046-6673 Online ISSN - 1533-3450

Powered by HighWire