We describe here a novel WT1 gene mutation, i.e. a point mutation at intron 7 (+2) in both the tumor and the germline cells of a patient with Wilms' tumor and congenital male genitourinary malformation, but without renal disorder.
We report a novel sequence variant (c.1012A>T) of the WT1 gene in exon 6 (p.R338X) in a 18-year-old girl with a history of Wilms' tumour, minor gonadal changes and relatively late-onset nephropathy.
We hypothesize that this type of mutation (read-through), which leads to an elongated, but otherwise unchanged, WT1 protein, may be associated with incomplete penetrance and a relatively late onset of both Wilms tumor and nephropathy in this family.
Although these syndromes are genetic models of nephropathy and the mutations of WT1 gene are characterized in these patients the mechanism how mutations of WT1 gene affect the embryonic kidney adversely has not been elucidated.
Compared with tubular cells of normal subjects, tubular cells of humans with a variety of nephropathies and those of several mouse models of CKD expressed high levels of Wnt9a that colocalized with the senescence-related protein p16<sup>INK4A</sup> Wnt9a expression level correlated with the extent of renal fibrosis, decline of eGFR, and expression of p16<sup>INK4A</sup> Furthermore, ectopic expression of Wnt9a after ischemia-reperfusion injury (IRI) induced activation of <i>β</i>-catenin and exacerbated renal fibrosis.
Wnt4 expression is induced throughout the collecting ducts in four murine models of renal injury that produce tubulointerstitial fibrosis: folic acid-induced nephropathy, unilateral ureteral obstruction, renal needle puncture, and genetic polycystic kidney disease.
The clinical significance of increase in WNT10A was evaluated by performing an immunohistochemical association study in a 19-year follow-up cohort comprising 284 RCC and 267 benign renal disease (BRD) patients.
SIRT1, a NAD<sup>+</sup>-dependent protein deacetylase, deacetylates the p65 of NF-κB and shows protective effects in kidney disorders. miR-373 directly targets the 3'UTR of SIRT1.
We performed a comprehensive genetic analysis for major inherited kidney diseases with next-generation sequencing including the genes responsible for PHA2 (WNK1, WNK4, KLHL3, and CUL3).
Furthermore, we found that conditional knockout of downstream Smad2 in TECs protected against loss of renal function, and alleviated p53-mediated cell apoptosis, RIPK-mediated necroptosis and p65 NF-κB-driven renal inflammation in cisplatin nephropathy.