NPHS2 screening with SURVEYOR in Hellenic children with steroid-resistant nephrotic syndrome
| Autor: | Voskarides, Konstantinos, Makariou, Christiana, Papagregoriou, Gregory N., Stergiou, Nikolaos, Printza, Nikoleta G., Alexopoulos, Efstathios, Elia, Avraam, Papachristou, Fotios Th, Pierides, Alkis M., Georgaki, Eleni, Constantinou-Deltas, Constantinos D. |
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| Přispěvatelé: | Constantinou-Deltas, Constantinos D. [0000-0001-5549-9169] |
| Rok vydání: | 2008 |
| Předmět: |
Male
Nephrotic Syndrome polymerase chain reaction Drug Resistance Gastroenterology endonuclease Exon genetic variability genetic polymorphism DNA denaturation exon gene mutation Child clinical article Proteinuria medicine.diagnostic_test biology Greece nephrotic syndrome proliferative glomerulonephritis pathogenesis steroid Intracellular Signaling Peptides and Proteins Glomerulonephritis genetic screening cohort analysis female priority journal Nephrology WT1 protein Slit diaphragm histopathology Female Steroids medicine.symptom focal glomerulosclerosis mutational analysis medicine.medical_specialty kidney biopsy Molecular Sequence Data letter DNA sequence male Internal medicine medicine Humans controlled study human Genetic Testing Genetic testing Base Sequence business.industry amplicon Membrane Proteins DNA medicine.disease human tissue Steroid-resistant nephrotic syndrome Endocrinology Pediatrics Perinatology and Child Health Cyprus Podocin biology.protein business Nephrotic syndrome podocin |
| Zdroj: | Pediatric Nephrology Pediatr.Nephrol. |
| ISSN: | 0931-041X |
| Popis: | Sirs,The idiopathic nephrotic syndrome is a common clinico-pathological entity characterized by massive proteinuria,hypoalbuminaemia, hyperlipidaemia, oedema, and variousglomerular changes, occurring mainly in children in 15–20% of whom the condition is steroid-resistant. About 85%of patients with steroid-resistant nephrotic syndrome(SRNS) exhibit renal histology of focal segmental glomer-ulosclerosis (FSGS), and the rest exhibit mesangial prolif-erative glomerulonephritis (MsPGN) or other rarerhistological phenotypes [1]. Mutations in the NPHS2 gene,encoding podocin, which is one of the important proteins ofthe slit diaphragm, are a frequent cause of sporadic SRNSin children, occurring in 2.8–28% of the cases [2–4].Mutations in exons 8 and 9 of the WT1 gene have also beenreported (more frequently in girls) with isolated SRNS [5].Other genes that are responsible have been recentlyreported, accounting for rare cases of SRNS.Idiopathic nephrotic syndrome is a frequent glomerulardisease in Cyprus and Greece, where 15–20% of cases aresteroid resistant, in accordance with the literature. In thiswork we studied for the first time in Greece and Cyprus acohort of 24 children (ten boys, 14 girls) with SRNS. Renalhistology, based on 1–3 biopsies, showed changes in FSGSin 21 children and MsPGN in three children. We investi-gated these children at the molecular level by searching formutations in the NPHS2 and WT1 (exons 8 and 9) genes. Indoing so, we used, for the first time to our knowledge,SURVEYOR endonuclease (Transgenomic, UK), an en-zyme that cleaves double-stranded DNA at positions ofheteroduplex mismatches, as a method for identifyingmutations and/or polymorphic variants. For this, genomicsequences, amplified by polymerase chain reaction (PCR)and encompassing the exons, the consensus exon |
| Databáze: | OpenAIRE |
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