scholarly journals INF2 mutations often implicated in autosomal dominant focal segmental glomerulosclerosis

2011 ◽  
Vol 7 (4) ◽  
pp. 181-181 ◽  
Author(s):  
Rebecca Ireland
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Autosomal Dominant ◽  
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.

scholarly journals Recurrent autosomal-dominant focal segmental glomerulosclerosis

2006 ◽  
Vol 70 (9) ◽  
pp. 1664-1665 ◽  
Author(s):  
S. Sanna-Cherchi ◽  
D. Somenzi ◽  
M.L. Carnevali ◽  
F.P. Pilato ◽  
M. Carraro ◽  
...  
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Autosomal Dominant ◽  
Segmental Glomerulosclerosis

scholarly journals Mutations in INF2 Are a Major Cause of Autosomal Dominant Focal Segmental Glomerulosclerosis

2011 ◽  
Vol 22 (2) ◽  
pp. 239-245 ◽  
Author(s):  
Olivia Boyer ◽  
Geneviève Benoit ◽  
Olivier Gribouval ◽  
Fabien Nevo ◽  
Marie-Josèphe Tête ◽  
...  
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Autosomal Dominant ◽  
Segmental Glomerulosclerosis
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