Novel Mutations in NPHS2 Detected in Both Familial and Sporadic Steroid-Resistant Nephrotic Syndrome

• Published in: Journal of the American Society of Nephrology Vol. 13; no. 2; pp. 388 - 393
• Main Authors: Karle, Stephanie M., Uetz, Barbara, Ronner, Vera, Glaeser, Lisa, Hildebrandt, Friedhelm, Fuchshuber, Arno
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.02.2002
• Subjects: Adolescent; Amino Acid Sequence - genetics; Base Sequence - genetics; Biological and medical sciences; Child; Child, Preschool; DNA Mutational Analysis; DNA, Recombinant; Drug Resistance; Female; Frameshift Mutation; Glomerulonephritis; Haplotypes; Humans; Intracellular Signaling Peptides and Proteins; Male; Medical sciences; Membrane Proteins - genetics; Mutation - genetics; Mutation, Missense; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Nephrotic Syndrome - drug therapy; Nephrotic Syndrome - genetics; Pedigree; Polymorphism, Genetic; Steroids - therapeutic use; Glomerulonephritis; Kidney disease; Human; Steroid; Treatment resistance; Urinary system disease; Sporadic; Terminal stage; Nephrotic syndrome; Chromosome 1; Gene; Autosomal character; Renal failure; Family environment; Recessive character; Mutation
• ISSN: 1046-6673
• DOI: 10.1681/ASN.V132388

Autosomal recessive steroid-resistant nephrotic syndrome (SRINS) belongs to the heterogeneous group of familial nephrotic syndrome and represents a frequent cause of end-stage renal disease in childhood. This kidney disorder is characterized by early onset of proteinuria, progression to end-stage renal disease, and histologic findings of focal segmental glomerulosclerosis, minimal change nephrotic syndrome, or both. A causative gene, NPHS2, has been mapped to chromosome 1q25-q31 and was recently identified by positional cloning. This study reports five novel NPHS2 mutations: A284V, R196P, V290M, IVS4-1G-->T, and 460-467insT in 12 (46%) of 26 multiplex families and in 7 (28%) of 25 single patients with the clinical diagnosis of a SRINS. Because NPHS2 mutations were found in nearly 30% of these patients with "sporadic" SRINS, mutational analysis should also be performed in these patients. Besides better classification of the disease entity, identification of NPHS2 mutations may save some of these patients from unnecessary steroid treatment and also permit the prediction of absence of disease recurrence after kidney transplantation.