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Citations to this article

ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling
Heon Yung Gee, … , Edgar A. Otto, Friedhelm Hildebrandt
Heon Yung Gee, … , Edgar A. Otto, Friedhelm Hildebrandt
Published July 8, 2013
Citation Information: J Clin Invest. 2013;123(8):3243-3253. https://doi.org/10.1172/JCI69134.
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Research Article Article has an altmetric score of 17

ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling

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Abstract

Nephrotic syndrome (NS) is divided into steroid-sensitive (SSNS) and -resistant (SRNS) variants. SRNS causes end-stage kidney disease, which cannot be cured. While the disease mechanisms of NS are not well understood, genetic mapping studies suggest a multitude of unknown single-gene causes. We combined homozygosity mapping with whole-exome resequencing and identified an ARHGDIA mutation that causes SRNS. We demonstrated that ARHGDIA is in a complex with RHO GTPases and is prominently expressed in podocytes of rat glomeruli. ARHGDIA mutations (R120X and G173V) from individuals with SRNS abrogated interaction with RHO GTPases and increased active GTP-bound RAC1 and CDC42, but not RHOA, indicating that RAC1 and CDC42 are more relevant to the pathogenesis of this SRNS variant than RHOA. Moreover, the mutations enhanced migration of cultured human podocytes; however, enhanced migration was reversed by treatment with RAC1 inhibitors. The nephrotic phenotype was recapitulated in arhgdia-deficient zebrafish. RAC1 inhibitors were partially effective in ameliorating arhgdia-associated defects. These findings identify a single-gene cause of NS and reveal that RHO GTPase signaling is a pathogenic mediator of SRNS.

Authors

Heon Yung Gee, Pawaree Saisawat, Shazia Ashraf, Toby W. Hurd, Virginia Vega-Warner, Humphrey Fang, Bodo B. Beck, Olivier Gribouval, Weibin Zhou, Katrina A. Diaz, Sivakumar Natarajan, Roger C. Wiggins, Svjetlana Lovric, Gil Chernin, Dominik S. Schoeb, Bugsu Ovunc, Yaacov Frishberg, Neveen A. Soliman, Hanan M. Fathy, Heike Goebel, Julia Hoefele, Lutz T. Weber, Jeffrey W. Innis, Christian Faul, Zhe Han, Joseph Washburn, Corinne Antignac, Shawn Levy, Edgar A. Otto, Friedhelm Hildebrandt

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2009 Total
Citations: 5 3 5 9 17 8 13 13 18 22 9 10 3 1 136
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2022 (9)

Title and authors Publication Year
Drosophila melanogaster: a simple genetic model of kidney structure, function and disease
J Dow, M Simons, M Romero
Nature Reviews Nephrology 2022
Mechanisms of podocyte injury and implications for diabetic nephropathy
F Barutta, S Bellini, G Gruden
Clinical Science 2022
Using Drosophila Nephrocytes to Understand the Formation and Maintenance of the Podocyte Slit Diaphragm
van de Leemput J, Wen P, Han Z
Frontiers in Cell and Developmental Biology 2022
Impact of klotho on the expression of SRGAP2a in podocytes in diabetic nephropathy
Jin D, Jia M, Xie Y, Lin L, Qiu H, Lu G
BMC Nephrology 2022
High detection rate for disease-causing variants in a cohort of 30 Iranian pediatric steroid resistant nephrotic syndrome cases
Najafi M, Riedhammer KM, Rad A, Torbati PN, Berutti R, Schüle I, Schroda S, Meitinger T, Ćomić J, Bojd SS, Baranzehi T, Shojaei A, Azarfar A, Khazaei MR, Köttgen A, Backofen R, Karimiani EG, Hoefele J, Schmidts M
Frontiers in Pediatrics 2022
Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis.
Hussain HMJ, Cai Y, Weng Q, Tong J, Aftab A, Jin Y, Liu J, Yu S, Fang Z, Du W, Pan X, Ren H, Xie J
Human genomics 2022
Renal FGF23 signaling depends on redox protein Memo1 and promotes orthovanadate-sensitive protein phosphotyrosyl phosphatase activity.
Bartos K, Ramakrishnan SK, Braga-Lagache S, Hänzi B, Durussel F, Prakash Sridharan A, Zhu Y, Sheehan D, Hynes NE, Bonny O, Moor MB
Journal of Cell Communication and Signaling 2022
Ion channels and channelopathies in glomeruli
Staruschenko A, Ma R, Palygin O, Dryer SE
Physiological reviews 2022
Model organisms for functional validation in genetic renal disease
Boettcher S, Simons M
medizinische genetik 2022

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