Mutations in WT1 in boys with sporadic isolated steroid-resistant nephrotic syndrome

Yang, Yuhui; Zhao, Fei; Tu, Xiang-ong; Yu, Zhongxin

doi:10.4238/gmr.15017559

Cited by 6 publications

(6 citation statements)

References 23 publications

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“…The mean age at diagnosis of Frasier syndrome was estimated to be 16.3±2.3 years, 2 , 15 , 20 which is also the age at which the diagnosis of end-stage renal disease is often made, although the onset of renal symptoms of proteinuria, edema and hypertension typically begins between 2 and 10 years of age. 1 , 2 , 6 , 9 , 10 , 19 , 20 This patient had a similar picture; since his childhood he was often in hospital for reasons of facial oedema and alteration of the renal function. This prompted the abdominal ultrasound revealing a decrease in kidney size of kidneys, and allowed the diagnosis of preterminal renal insufficiency at age 16.…”

Section: Discussionmentioning

confidence: 82%

Suspicion of Frasier’s Syndrome in the Nephrology Unit of the State University Hospital of Haiti: Case Study and Review of Literature

Paul¹,

Louis²,

Desravines³

et al. 2021

IMCRJ

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Objective Frasier syndrome is a rare genetic nephropathy characterized by the presence of progressive glomerulopathy with proteinuria associated with male pseudo hermaphroditism. This case study described a picture of a young boy where the clinical suspicion context reminded the Frasier syndrome. To our knowledge, this case is the first described in Haiti. Case Study This is a 19-year-old young phenotypically male, born with a genital anomaly, was seen on referral at the nephrology/dialysis unit of the internal medicine department of the State University Hospital of Haiti for evaluation and follow-up. Insidious progression of symptoms had occurred over 3 years. Over three months of outpatient follow-up, he had four sets of renal labs drawn, and all showed impaired renal function. At the ultrasound, a bilateral cryptorchidism is described in the inguinal, and presence of functional ovaries with follicles of variable size scattered in the parenchyma. So, in the light of these anamnestic, clinical and paraclinical findings, we concluded to the diagnosis of end-stage renal failure by progressive glomerulopathy in a context of Frasier’s syndrome. Conclusion With any clinical picture consisting of genital anomalies at birth, renal symptomatology during childhood and the diagnosis of renal failure during adolescence, rare genetic nephropathies, such as Frasier syndrome must be considered.

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Section: Discussionmentioning

confidence: 82%

Suspicion of Frasier’s Syndrome in the Nephrology Unit of the State University Hospital of Haiti: Case Study and Review of Literature

Paul¹,

Louis²,

Desravines³

et al. 2021

IMCRJ

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“…It has great value on the diagnosis of podocyte lesion [ 43 ]. Defects in WT-1 are the cause of multiple renal diseases, such as nephrotic syndrome type 4, Denys-Drash syndrome, and Frasier syndrome [ 44 – 46 ]. What is more, fibrotic-related proteins α -SMA, fibronectin, and collagen I were increased in HG-treated MPC5 cells, which is consistent with previous reports [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miR-17~92 Cluster Ameliorates High Glucose-Induced Podocyte Damage

Fan

Hao

et al. 2020

Mediators of Inflammation

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The loss and damage of podocytes is an early feature of diabetic nephropathy (DN). The miR-17∼92 cluster was dysregulated in diabetic and polycystic kidney disease patients, but its role in DN is unclear. Hence, an in vitro study on the high glucose- (HG-) treated mouse podocytes (MPC5) was designed to elucidate the effect of miR-17∼92 cluster downregulation on cell viability, apoptosis, inflammation, fibrosis, and podocyte function. The results suggested that the miR-17∼92 cluster members miR-17-5p, miR-18a, miR-19a, miR-19b, miR-20a, and miR-92a were upregulated in the renal biopsy tissue of DN patients and HG-treated MPC5. The downregulation of the miR-17∼92 cluster effectively suppressed the cell apoptosis, inflammation, fibrosis, and podocyte dysfunction in HG-stimulated MPC5 cells. The bioinformatics analysis and rescue experiments showed that ABCA1 (ATP-binding cassette transporter A1) is an effector of the miR-17~92 cluster. Silence of ABCA1 inhibited the protective effect of the miR-17∼92 cluster downregulation on podocyte damage. In summary, this research indicated that the downregulation of the miR-17∼92 cluster ameliorates HG-induced podocyte damage via targeting ABCA1.

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“…Based on their steroid responsiveness, patients are classified as steroid-sensitive and steroid-resistant. Genetic mutations that affect glomerular podocyte function, such as NPHS1, NPHS2 , and WT1 [ 133 – 137 ], account for most steroid-resistant cases and patients with genetic forms of steroid-resistance are less responsive to immunotherapeutic drugs. The circulating factor, soluble urokinase receptor, has been considered a cause for the development of SRNS [ 138 , 139 ].…”

Section: The Effects Of Glucocorticoid Therapy On Nephrotic Syndromentioning

confidence: 99%

The Role of Glucocorticoid Receptors in Podocytes and Nephrotic Syndrome

Zhao

Hwang

Kao

2018

Nuclear Receptor Research

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Glucocorticoid receptor (GC), a founding member of the nuclear hormone receptor superfamily, is a glucocorticoid-activated transcription factor that regulates gene expression and controls the development and homeostasis of human podocytes. Synthetic glucocorticoids are the standard treatment regimens for proteinuria (protein in the urine) and nephrotic syndrome (NS) caused by kidney diseases. These include minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and immunoglobulin A nephropathy (IgAN) or subsequent complications due to diabetes mellitus or HIV infection. However, unwanted side effects and steroid-resistance remain major issues for their long-term use. Furthermore, the mechanism by which glucocorticoids elicit their renoprotective activity in podocyte and glomeruli is poorly understood. Podocytes are highly differentiated epithelial cells that contribute to the integrity of kidney glomerular filtration barrier. Injury or loss of podocytes leads to proteinuria and nephrotic syndrome. Recent studies in multiple experimental models have begun to explore the mechanism of GC action in podocytes. This review will discuss progress in our understanding of the role of glucocorticoid receptor and glucocorticoids in podocyte physiology and their renoprotective activity in nephrotic syndrome.

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Mutations in WT1 in boys with sporadic isolated steroid-resistant nephrotic syndrome

Cited by 6 publications

References 23 publications

Suspicion of Frasier’s Syndrome in the Nephrology Unit of the State University Hospital of Haiti: Case Study and Review of Literature

Suspicion of Frasier’s Syndrome in the Nephrology Unit of the State University Hospital of Haiti: Case Study and Review of Literature

Inhibition of miR-17~92 Cluster Ameliorates High Glucose-Induced Podocyte Damage

The Role of Glucocorticoid Receptors in Podocytes and Nephrotic Syndrome

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