Prednisone/cyclophos-phamide treatment in adult-onset autosomal dominant familial focal segmental glomerulosclerosis (FSGS 1)

2006 ◽  
Vol 65 (06) ◽  
pp. 461-462 ◽  
Author(s):  
L. Grcevska ◽  
S. Dzikova ◽  
G. Petrusevska ◽  
M. Polenakovic
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Autosomal Dominant ◽  
Adult Onset ◽  
Segmental Glomerulosclerosis

scholarly journals Importance of Genetic Diagnostics in Adult-Onset Focal Segmental Glomerulosclerosis

Nephron ◽  
2019 ◽  
Vol 142 (4) ◽  
pp. 351-358 ◽  
Author(s):  
Rozemarijn Snoek ◽  
Tri Q. Nguyen ◽  
Bert van der Zwaag ◽  
Arjan D. van Zuilen ◽  
Hannah M.E. Kruis ◽  
...  
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Genetic Diagnostics ◽  
Adult Onset ◽  
Segmental Glomerulosclerosis

Molecular Analysis of NPHS2 and ACTN4 Genes in a Series of 33 Italian Patients Affected by Adult-Onset Nonfamilial Focal Segmental Glomerulosclerosis

2004 ◽  
Vol 99 (2) ◽  
pp. c31-c36 ◽  
Author(s):  
Filippo Aucella ◽  
Patrizia De Bonis ◽  
Giuseppe Gatta ◽  
Lucia Anna Muscarella ◽  
Mimmo Vigilante ◽  
...  
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Molecular Analysis ◽  
Adult Onset ◽  
Segmental Glomerulosclerosis

scholarly journals First identification of PODXL nonsense mutations in autosomal dominant focal segmental glomerulosclerosis

2019 ◽  
Vol 133 (1) ◽  
pp. 9-21 ◽  
Author(s):  
Fu-Jun Lin ◽  
Lei Yao ◽  
Xue-Qing Hu ◽  
Fan Bian ◽  
Gang Ji ◽  
...  
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Autosomal Dominant ◽  
In Vitro Study ◽  
Peripheral Blood Cell ◽  
Fiber Formation ◽  
Causative Role ◽  
Gene Encoding ◽  
Nonsense Mutations ◽  
Segmental Glomerulosclerosis

Abstract Recently, a novel heterozygous missense mutation c.T1421G (p. L474R) in the PODXL gene encoding podocalyxin was identified in an autosomal dominant focal segmental glomerulosclerosis (AD-FSGS) pedigree. However, this PODXL mutation appeared not to impair podocalyxin function, and it is necessary to identify new PODXL mutations and determine their causative role for FSGS. In the present study, we report the identification of a heterozygous nonsense PODXL mutation (c.C976T; p. Arg326X) in a Chinese pedigree featured by proteinuria and renal insufficiency with AD inheritance by whole exome sequencing (WES). Total mRNA and PODXL protein abundance were decreased in available peripheral blood cell samples of two affected patients undergoing hemodialysis, compared with those in healthy controls and hemodialysis controls without PODXL mutation. We identified another novel PODXL heterozygous nonsense mutation (c.C1133G; p.Ser378X) in a British–Indian pedigree of AD-FSGS by WES. In vitro study showed that, human embryonic kidney 293T cells transfected with the pEGFP-PODXL-Arg326X or pEGFP-PODXL-Ser378X plasmid expressed significantly lower mRNA and PODXL protein compared with cells transfected with the wild-type plasmid. Blocking nonsense-mediated mRNA decay (NMD) significantly restored the amount of mutant mRNA and PODXL proteins, which indicated that the pathogenic effect of PODXL nonsense mutations is likely due to NMD, resulting in podocalyxin deficiency. Functional consequences caused by the PODXL nonsense mutations were inferred by siRNA knockdown in cultured podocytes and podocalyxin down-regulation by siRNA resulted in decreased RhoA and ezrin activities, cell migration and stress fiber formation. Our results provided new data implicating heterozygous PODXL nonsense mutations in the development of FSGS.

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