Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nephrotic syndrome is defined as the association of massive proteinuria, hypoalbuminaemia, edema, and hyperlipidemia. It is separated to steroid-sensitive or steroid-resistant (SRNS) forms in respect to the response to intensive steroid therapy. SRNS usually progresses to end-stage renal failure. According to the North American Pediatric Renal Trials and Collaborative Studies SRNS constitutes the second most frequent cause of ESRD in the first two decades of life. Unfortunately, there is no curative treatment for majority of patients. Majority of the SRNS patients have the histologic picture of focal segmental glomerulosclerosis. Interestingly, the risk of recurrence in the kidney graft in patients with hereditary SRNS is lower than in those who do not have genetic background. The etiology and pathogenesis of SRSN has remained enigma for decades. The discovery of 39 dominant or recessive SRNS genes enabled better understanding of the function of the glomerular podocytes and slit membrane. Hildebrandt's group has shown that 85% of the SRNS cases with onset by 3 months of age and 66% with onset by 1 year of age can be explained by recessive mutations in one of four genes only (NPHS1, NPHS2, LAMB2, or WT1). The same group used modern diagnostic techniques such as the next generation sequencing and tested a large international cohort of SRNS patients (n = 1783 families). The diagnostic panel included 21 genes with a recessive mode of inheritance and 6 genes with a dominant mode of inheritance. Single-gene cause was detected in 29.5% (526 of 1783) of the families with SRNS that manifested before 25 years of age. The identification of causative single-gene mutations may have important therapeutic consequences in some cases. This is very important for patients who carry mutations in a gene of coenzyme Q10 biosynthesis (COQ2, COQ6, ADCK4, or PDSS2). In these patients the treatment with coenzyme Q10 may be indicated. Also, patients with recessive mutations in PLCE1 may respond fully to the treatment with steroids or cyclosporine A. The patients with CUBN may benefit the treatment with vitamin B12. The detection of causative mutations may also be very important for familial genetic counseling and for prenatal diagnosis.
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PMID:Steroid Resistant Nephrotic Syndrome-Genetic Consideration. 2744 91

BACKGROUND Nephrotic syndrome (NS) is a common chronic kidney disease in children characterized by a group of clinical symptoms such as massive proteinuria, hypoproteinemia, high edema, and hyperlipidemia. Despite the tremendous efforts already made, the diagnosis for nephrotic syndrome still remains poor in children. MATERIAL AND METHODS The blood samples from 30 healthy children and 30 children with nephrotic syndrome were collected. The expression of H19 and ADCK4 (which are genes recently identified to play key roles in the development of nephrotic syndrome) in peripheral blood mononuclear cells (PBMCs), were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The expression of ADCK4 was also detected by RT-qPCR or western blot when H19 was overexpressed or knocked down in human primary renal podocytes. Luciferase activity analysis was performed to measure whether H19 could regulate the promoter activity of ADCK4. RNA pull-down. In addition, mass spectrometry assay was used to find the transcription factor which could bind with H19, and RNA immunoprecipitation assay (RIPA) analysis was done to further confirm the interaction between H19 and candidate transcription factor. RESULTS Long noncoding RNA H19 (lncRNA H19) expression was downregulated in PBMCs of children with nephrotic syndrome. ADCK4 was also downregulated. In human primary renal podocytes, overexpression of H19 promoted the expression of ADCK4, while H19 knockdown inhibited it. Furthermore, our study demonstrated that H19 could regulate the promoter activity of ADCK4. Using RNA pull-down and mass spectrometry technology, we found the transcription factor-THAP1 could bind with H19, and the interaction between them was further confirmed by RIPA analysis. CONCLUSIONS H19 expression in blood samples may be a novel marker of the diagnosis of nephrotic syndrome in children.
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PMID:Absence of Long Noncoding RNA H19 Promotes Childhood Nephrotic Syndrome through Inhibiting ADCK4 Signal. 3248 87