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Clinical features and outcome of childhood minimal change nephrotic syndrome: is genetics involved?

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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.

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Acknowledgements

This work was supported by grants from the Finnish Academy, the Sigrid Juselius Foundation, Pediatric Research Foundation, and Helsinki University Central Hospital Research Fund.

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Authors and Affiliations

  1. Hospital for Children and Adolescents and Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, Room B526b, 00290, Helsinki, Finland

    Anne-Tiina Lahdenkari, Maija Suvanto, Eero Kajantie, Olli Koskimies & Hannu Jalanko

  2. Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland

    Eero Kajantie

  3. National Public Health Institute, Department of Molecular Medicine, Helsinki, Finland

    Marjo Kestilä

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  1. Anne-Tiina Lahdenkari
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  2. Maija Suvanto
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  6. Hannu Jalanko
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Correspondence to Anne-Tiina Lahdenkari.

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Anne-Tiina Lahdenkari and Maija Suvanto contributed equally

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Lahdenkari, AT., Suvanto, M., Kajantie, E. et al. Clinical features and outcome of childhood minimal change nephrotic syndrome: is genetics involved?. Pediatr Nephrol 20, 1073–1080 (2005). https://doi.org/10.1007/s00467-005-1965-y

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  • DOI: https://doi.org/10.1007/s00467-005-1965-y

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