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Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome

Authors
 Jillian K Warejko  ;  Weizhen Tan  ;  Ankana Daga  ;  David Schapiro  ;  Jennifer A Lawson  ;  Shirlee Shril  ;  Svjetlana Lovric  ;  Shazia Ashraf  ;  Jia Rao  ;  Tobias Hermle  ;  Tilman Jobst-Schwan  ;  Eugen Widmeier  ;  Amar J Majmundar  ;  Ronen Schneider  ;  Heon Yung Gee  ;  J Magdalena Schmidt  ;  Asaf Vivante  ;  Amelie T van der Ven  ;  Hadas Ityel  ;  Jing Chen  ;  Carolin E Sadowski  ;  Stefan Kohl  ;  Werner L Pabst  ;  Makiko Nakayama  ;  Michael J G Somers  ;  Nancy M Rodig  ;  Ghaleb Daouk  ;  Michelle Baum  ;  Deborah R Stein  ;  Michael A Ferguson  ;  Avram Z Traum  ;  Neveen A Soliman  ;  Jameela A Kari  ;  Sherif El Desoky  ;  Hanan Fathy  ;  Martin Zenker  ;  Sevcan A Bakkaloglu  ;  Dominik Muller  ;  Aytul Noyan  ;  Fatih Ozaltin  ;  Melissa A Cadnapaphornchai  ;  Seema Hashmi  ;  Jeffrey Hopcian  ;  Jeffrey B Kopp  ;  Nadine Benador  ;  Detlef Bockenhauer  ;  Radovan Bogdanovic  ;  Natasa Stajic  ;  Gil Chernin  ;  Robert Ettenger  ;  Henry Fehrenbach  ;  Markus Kemper  ;  Reyner Loza Munarriz  ;  Ludmila Podracka  ;  Rainer Buscher  ;  Erkin Serdaroglu  ;  Velibor Tasic  ;  Shrikant Mane  ;  Richard P Lifton  ;  Daniela A Braun  ;  Friedhelm Hildebrandt 
Citation
 CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol.13(1) : 53-62, 2018 
Journal Title
 CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 
ISSN
 1555-9041 
Issue Date
2018
Keywords
Child ; Exome ; Humans ; Chronic Kidney Failure ; Mutation ; congenital Nephrosis ; Phenotype ; Chronic Renal Insufficiency ; genetic renal disease ; kidney transplantation ; molecular genetics ; nephrotic syndrome ; pediatric
Abstract
BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome overwhelmingly progresses to ESRD. More than 30 monogenic genes have been identified to cause steroid-resistant nephrotic syndrome. We previously detected causative mutations using targeted panel sequencing in 30% of patients with steroid-resistant nephrotic syndrome. Panel sequencing has a number of limitations when compared with whole exome sequencing. We employed whole exome sequencing to detect monogenic causes of steroid-resistant nephrotic syndrome in an international cohort of 300 families. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Three hundred thirty-five individuals with steroid-resistant nephrotic syndrome from 300 families were recruited from April of 1998 to June of 2016. Age of onset was restricted to <25 years of age. Exome data were evaluated for 33 known monogenic steroid-resistant nephrotic syndrome genes. RESULTS: In 74 of 300 families (25%), we identified a causative mutation in one of 20 genes known to cause steroid-resistant nephrotic syndrome. In 11 families (3.7%), we detected a mutation in a gene that causes a phenocopy of steroid-resistant nephrotic syndrome. This is consistent with our previously published identification of mutations using a panel approach. We detected a causative mutation in a known steroid-resistant nephrotic syndrome gene in 38% of consanguineous families and in 13% of nonconsanguineous families, and 48% of children with congenital nephrotic syndrome. A total of 68 different mutations were detected in 20 of 33 steroid-resistant nephrotic syndrome genes. Fifteen of these mutations were novel. NPHS1, PLCE1, NPHS2, and SMARCAL1 were the most common genes in which we detected a mutation. In another 28% of families, we detected mutations in one or more candidate genes for steroid-resistant nephrotic syndrome. CONCLUSIONS: Whole exome sequencing is a sensitive approach toward diagnosis of monogenic causes of steroid-resistant nephrotic syndrome. A molecular genetic diagnosis of steroid-resistant nephrotic syndrome may have important consequences for the management of treatment and kidney transplantation in steroid-resistant nephrotic syndrome.
Full Text
http://cjasn.asnjournals.org/content/13/1/53
DOI
10.2215/cjn.04120417
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162064
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