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

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A Single-Gene Cause in 29.5% of Cases of Steroid-Resistant Nephrotic Syndrome. / Sadowski, Carolin E; Lovric, Svjetlana; Ashraf, Shazia; Pabst, Werner L; Gee, Heon Yung; Kohl, Stefan; Engelmann, Susanne; Vega-Warner, Virginia; Fang, Humphrey; Halbritter, Jan; Somers, Michael J; Tan, Weizhen; Shril, Shirlee; Fessi, Inès; Lifton, Richard P; Bockenhauer, Detlef; El-Desoky, Sherif; Kari, Jameela A; Zenker, Martin; Kemper, Markus Josef; Mueller, Dominik; Fathy, Hanan M; Soliman, Neveen A; Hildebrandt, Friedhelm; the SRNS Study Group.

in: J AM SOC NEPHROL, Jahrgang 26, Nr. 6, 06.2015, S. 1279-1289 .

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Sadowski, CE, Lovric, S, Ashraf, S, Pabst, WL, Gee, HY, Kohl, S, Engelmann, S, Vega-Warner, V, Fang, H, Halbritter, J, Somers, MJ, Tan, W, Shril, S, Fessi, I, Lifton, RP, Bockenhauer, D, El-Desoky, S, Kari, JA, Zenker, M, Kemper, MJ, Mueller, D, Fathy, HM, Soliman, NA, Hildebrandt, F & the SRNS Study Group 2015, 'A Single-Gene Cause in 29.5% of Cases of Steroid-Resistant Nephrotic Syndrome', J AM SOC NEPHROL, Jg. 26, Nr. 6, S. 1279-1289 . https://doi.org/10.1681/ASN.2014050489

APA

Sadowski, C. E., Lovric, S., Ashraf, S., Pabst, W. L., Gee, H. Y., Kohl, S., Engelmann, S., Vega-Warner, V., Fang, H., Halbritter, J., Somers, M. J., Tan, W., Shril, S., Fessi, I., Lifton, R. P., Bockenhauer, D., El-Desoky, S., Kari, J. A., Zenker, M., ... the SRNS Study Group (2015). A Single-Gene Cause in 29.5% of Cases of Steroid-Resistant Nephrotic Syndrome. J AM SOC NEPHROL, 26(6), 1279-1289 . https://doi.org/10.1681/ASN.2014050489

Vancouver

Sadowski CE, Lovric S, Ashraf S, Pabst WL, Gee HY, Kohl S et al. A Single-Gene Cause in 29.5% of Cases of Steroid-Resistant Nephrotic Syndrome. J AM SOC NEPHROL. 2015 Jun;26(6):1279-1289 . https://doi.org/10.1681/ASN.2014050489

Bibtex

@article{cf5e35764d6444458d1af3c5de60079f,
title = "A Single-Gene Cause in 29.5% of Cases of Steroid-Resistant Nephrotic Syndrome",
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.",
author = "Sadowski, {Carolin E} and Svjetlana Lovric and Shazia Ashraf and Pabst, {Werner L} and Gee, {Heon Yung} and Stefan Kohl and Susanne Engelmann and Virginia Vega-Warner and Humphrey Fang and Jan Halbritter and Somers, {Michael J} and Weizhen Tan and Shirlee Shril and In{\`e}s Fessi and Lifton, {Richard P} and Detlef Bockenhauer and Sherif El-Desoky and Kari, {Jameela A} and Martin Zenker and Kemper, {Markus Josef} and Dominik Mueller and Fathy, {Hanan M} and Soliman, {Neveen A} and Friedhelm Hildebrandt and {the SRNS Study Group}",
note = "Copyright {\textcopyright} 2014 by the American Society of Nephrology.",
year = "2015",
month = jun,
doi = "10.1681/ASN.2014050489",
language = "English",
volume = "26",
pages = "1279--1289 ",
journal = "J AM SOC NEPHROL",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "6",

}

RIS

TY - JOUR

T1 - A Single-Gene Cause in 29.5% of Cases of Steroid-Resistant Nephrotic Syndrome

AU - Sadowski, Carolin E

AU - Lovric, Svjetlana

AU - Ashraf, Shazia

AU - Pabst, Werner L

AU - Gee, Heon Yung

AU - Kohl, Stefan

AU - Engelmann, Susanne

AU - Vega-Warner, Virginia

AU - Fang, Humphrey

AU - Halbritter, Jan

AU - Somers, Michael J

AU - Tan, Weizhen

AU - Shril, Shirlee

AU - Fessi, Inès

AU - Lifton, Richard P

AU - Bockenhauer, Detlef

AU - El-Desoky, Sherif

AU - Kari, Jameela A

AU - Zenker, Martin

AU - Kemper, Markus Josef

AU - Mueller, Dominik

AU - Fathy, Hanan M

AU - Soliman, Neveen A

AU - Hildebrandt, Friedhelm

AU - the SRNS Study Group

N1 - Copyright © 2014 by the American Society of Nephrology.

PY - 2015/6

Y1 - 2015/6

N2 - 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.

AB - 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.

U2 - 10.1681/ASN.2014050489

DO - 10.1681/ASN.2014050489

M3 - SCORING: Journal article

C2 - 25349199

VL - 26

SP - 1279

EP - 1289

JO - J AM SOC NEPHROL

JF - J AM SOC NEPHROL

SN - 1046-6673

IS - 6

ER -