title: Clinical features and outcome of childhood minimal change nephrotic syndrome: is genetics involved?
abstract: The pathogenesis of minimal change nephrotic syndrome (MCNS) is still unknown. We performed a clinical and genetic evaluation of 104 adults (mean age 35 years) who presented with MCNS in childhood (mean follow-up 30 years). Clinical data and the present health status were evaluated. Also, the genes encoding the four major slit diaphragm proteins, nephrin, podocin, Neph1 and CD2-associated protein were sequenced in 38 patients with MCNS of varying severity. MCNS presented at the mean age of 5 years, and 80% of the patients relapsed 1-28 (median 3) times during childhood. The 14 subjects (14%) who had proteinuric episodes still in adulthood had a refractory disease already as children. The participants did not show a strong tendency for allergy or immune diseases, and no familial clustering of MCNS was observed. The genetic analyses revealed heterozygous amino acid changes in nephrin and podocin in 10 of the 38 patients studied. On the other hand, the genes coding for Neph1 and CD2AP were highly conserved and no amino acid substitutions were detected. In conclusion, MCNS is a multifactorial disease, in which genetics play a minor role. Allelic variants of the podocyte proteins may, however, modify the phenotype in occasional individuals.
authors.affiliation: Hospital for Children and Adolescents and Biomedicum Helsinki, University of Helsinki, Finland. anne-tiina.lahdenkari@hus.fi
authors.forename: Anne-Tiina
authors.initials: AT
authors.lastname: Lahdenkari
authors.forename: Maija
authors.initials: M
authors.lastname: Suvanto
authors.forename: Eero
authors.initials: E
authors.lastname: Kajantie
authors.forename: Olli
authors.initials: O
authors.lastname: Koskimies
authors.forename: Marjo
authors.initials: M
authors.lastname: Kestilä
authors.forename: Hannu
authors.initials: H
authors.lastname: Jalanko
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D003404:Creatinine / Q000097:blood; D003598:Cytoskeletal Proteins; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009402:Nephrosis, Lipoid / Q000209:etiology / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D011506:Proteins; C113267:nephrin; D003404:Creatinine