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Mutations in EMP2 cause childhood-onset nephrotic syndrome

Authors
 Heon Yung Gee  ;  Shazia Ashraf  ;  Xiaoyang Wan  ;  Virginia Vega-Warner  ;  Julian Esteve-Rudd  ;  Svjetlana Lovric  ;  Humphrey Fang  ;  Toby W. Hurd  ;  Carolin E. Sadowski  ;  Susan J. Allen  ;  Edgar A. Otto  ;  Emine Korkmaz  ;  Joseph Washburn  ;  Shawn Levy  ;  David S. Williams  ;  Sevcan A. Bakkaloglu  ;  Anna Zolotnitskaya  ;  Fatih Ozaltin  ;  Weibin Zhou  ;  Friedhelm Hildebrandt 
Citation
 AMERICAN JOURNAL OF HUMAN GENETICS, Vol.94(6) : 884-890, 2014 
Journal Title
 AMERICAN JOURNAL OF HUMAN GENETICS 
ISSN
 0002-9297 
Issue Date
2014
Abstract
Nephrotic syndrome (NS) is a genetically heterogeneous group of diseases that are divided into steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS). SRNS inevitably leads to end-stage kidney disease, and no curative treatment is available. To date, mutations in more than 24 genes have been described in Mendelian forms of SRNS; however, no Mendelian form of SSNS has been described. To identify a genetic form of SSNS, we performed homozygosity mapping, whole-exome sequencing, and multiplex PCR followed by next-generation sequencing. We thereby detected biallelic mutations in EMP2 (epithelial membrane protein 2) in four individuals from three unrelated families affected by SRNS or SSNS. We showed that EMP2 exclusively localized to glomeruli in the kidney. Knockdown of emp2 in zebrafish resulted in pericardial effusion, supporting the pathogenic role of mutated EMP2 in human NS. At the cellular level, we showed that knockdown of EMP2 in podocytes and endothelial cells resulted in an increased amount of CAVEOLIN-1 and decreased cell proliferation. Our data therefore identify EMP2 mutations as causing a recessive Mendelian form of SSNS.
Files in This Item:
T201406235.pdf Download
DOI
10.1016/j.ajhg.2014.04.010
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/22282913/139098
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