Clinical and Genetic Evaluation of Familial Steroid-Responsive Nephrotic Syndrome in Childhood

• Published in: Journal of the American Society of Nephrology Vol. 12; no. 2; pp. 374 - 378
• Main Authors: FUCHSHUBER, ARNO, GRIBOUVAL, OLIVIER, RONNER, VERA, KROISS, SABINE, KARLE, STEPHANIE, BRANDIS, MATTHIAS, HILDEBRANDT, FRIEDHELM
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.02.2001
• Subjects: Adolescent; Adrenal Cortex Hormones - therapeutic use; Biological and medical sciences; Child; Child, Preschool; Female; Genetic Linkage; Glomerulonephritis; Humans; Infant; Intracellular Signaling Peptides and Proteins; Male; Medical sciences; Membrane Proteins - genetics; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Nephrotic Syndrome - drug therapy; Nephrotic Syndrome - genetics; Human; Glomerulonephritis; Kidney disease; Steroid; Urinary system disease; Linkage; Nephrotic syndrome; Gene; Autosomal character; Cohort study; Adolescent; Recessive character; Genetics; Mutation; Child; Negative therapeutic reaction
• ISSN: 1046-6673
• DOI: 10.1681/ASN.V122374

Steroid-responsive idiopathic nephrotic syndrome (SSINS) is the most common form of nephrotic syndrome in childhood. This article reports a cohort of familial SSINS with disease onset in childhood. The clinical course in terms of age at onset, symptoms during the initial phase, renal morphology, and outcome was evaluated. Furthermore, linkage to NPHS2, the gene for autosomal-recessive steroid-resistant INS on chromosome 1, was examined. Two families with haplotypes consistent with linkage to NPHS2 were evaluated for mutations in the NPHS2 gene. Familial SSINS (32 patients from 15 families, minimal change NS in 12 of 12 biopsies) was found to be a clinically homogeneous entity. Interfamilial and intrafamilial variability with respect to the age at disease onset was low, indicating a strong genetic influence on disease onset. By linkage studies and mutational analysis, familial SSINS was found to be genetically distinct from NPHS2. This is the first report of a large cohort of familial SSINS. Exclusion of linkage to NPHS2 makes likely the existence of a distinct gene locus for SSINS.