title: Clinical and genetic evaluation of familial steroid-responsive nephrotic syndrome in childhood.
abstract: 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.
authors.affiliation: University Children's Hospital, Freiburg, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Fuchshuber
authors.affiliation: INSERM U423, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gribouval
authors.affiliation: University Children's Hospital, Freiburg, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Ronner
authors.affiliation: University Children's Hospital, Freiburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kroiss
authors.affiliation: University Children's Hospital, Freiburg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Karle
authors.affiliation: University Children's Hospital, Freiburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Brandis
authors.affiliation: University Children's Hospital, Freiburg, Germany.
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000235:genetics*
chemical_list: D000305:Adrenal Cortex Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein