Steroid-Resistant Nephrotic Syndrome (NPHS2) Contact details Introduction Molecular Genetics Service Nephrotic syndrome is a condition that is caused by any of a group of diseases that Level 6, York House damage the kidneys' filtering system, the glomeruli. The structure of the glomeruli 37 Queen Square prevents most protein from getting filtered through into the urine. Nephrotic syndrome London, WC1N 3BH is characterised by proteinuria (abnormally high loss of protein in the urine), T +44 (0) 20 7762 6888 albuminemia and hypercholesterolemia. Ultimately, there is rapid progression to end- F +44 (0) 20 7813 8578 stage renal disease where the kidneys are irreversibly damaged, resulting in death if untreated. Samples required Treatment is based on relieving symptoms, preventing complications and delaying • 5ml venous blood in plastic EDTA progressive kidney damage. Patients with nephrotic syndrome are typically treated bottles (>1ml from neonates) with steroids, of which about 80% have a good response; the rest are considered to • Prenatal testing must be arranged be steroid-resistant and may require renal transplant. One of the main features in in advance, through a Clinical steroid-resistant nephrotic syndrome (SRNS; MIM 600995) is focal segmental Genetics department if possible. glomerulosclerosis (FSGS). • Amniotic fluid or CV samples Mutations in the podocin gene, NPHS2, are associated with autosomal recessive should be sent to Cytogenetics for steroid-resistant nephrotic syndrome (SRNS), including focal segmental dissecting and culturing, with glomerulosclerosis (FSGS). Around half of familial forms and 10-30% of sporadic instructions to forward the sample to the Regional Molecular Genetics forms of SRNS are found to have NPHS2 mutations in both alleles. The gene is laboratory for analysis located on chromosome 1q25-31 and consists of 8 exons. • A completed DNA request card Referrals should accompany all samples Affected patients should fulfill the following criteria: Patient details Presence of nephrotic syndrome (serum albumin < 25g/l and urine albumin > 4 To facilitate accurate testing and mg/m2/h or urine albumin/creatinine ratio > 100 mg/mmol ), that is either: reporting please provide patient demographic details (full name, date of • resistant to treatment with steroids, or birth, address and ethnic origin), details of any relevant family history and full • present in the first 3 months of life, or contact details for the referring clinician • have a histological picture of FSGS on biopsy. Please also send a completed clinical information sheet (available on our laboratory website). Carrier testing can be offered to adult relatives of affected patients once a disease causing mutation has been identified. Prenatal testing Prenatal testing may be available for families following analysis of the affected proband - please contact the laboratory to discuss. Service offered Mutation screening of the 8 exons and exon/intron boundaries of the NPHS2 gene by Sanger sequencing. Target reporting time 8 weeks for routine screen in index case. 2 weeks for carrier testing using mutation specific tests. Please contact the laboratory for urgent cases. Version 6 .