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NPHS2 mutations in sporadic steroid-resistant nephrotic syndrome in Japanese children

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Abstract.

Podocin is an integral membrane protein encoded by NPHS2, which is mapped to 1q25–31 and is exclusively expressed in glomerular podocytes. NPHS2 mutations are responsible for autosomal recessive familial steroid-resistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal segmental glomerulosclerosis (FSGS), which is characterized by early childhood onset (age less than 6 years) and rapid progression to chronic renal insufficiency. This gene mutation is also responsible for an adolescent/adult onset form of autosomal recessive familial FSGS with heavy proteinuria. It has been demonstrated that sporadic SRNS and heavy proteinuria are also due to NPHS2 gene mutations. We isolated genomic DNA from 36 Japanese children with chronic renal insufficiency caused by SRNS or heavy proteinuria, and analyzed all eight exons and exon-intron boundaries of NPHS2 using the polymerase chain reaction and direct sequencing. The age at onset of disease was 3.9±0.5 years. There were 29 patients with SRNS and 7 with heavy proteinuria without nephrotic syndrome at the onset, but all patients developed chronic renal insufficiency 4.6±0.8 years after the onset. A new homozygous missense variant of NPHS2, G34E (G101A) in exon 1, was detected in 1 of 36 patients. However, this homozygous variant was also found in 1 of 44 normal controls, suggesting that the mutation is a polymorphism. Two silent variants (T954C and A1038G) in exon 8 of this gene were also identified in some of the patients and normal controls, indicating that the silent variants are also polymorphisms. There was no significant difference in the genotypic and allelic frequencies of T954C and A1038G polymorphisms between the patients and normal controls. In conclusion, NPHS2 gene mutations are not a major cause of chronic renal insufficiency caused by sporadic SRNS or heavy proteinuria in Japanese children.

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Acknowledgements.

This study was supported by a grant from The Study Group for Renal Anemia (to Dr. Iijima). The authors are grateful to Dr. H. Nishio for his helpful advice and to Miss K. Nishimoto for her technical assistance.

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Authors and Affiliations

  1. Faculty of Health Science, Kobe University Graduate School of Medicine, Kobe, Japan

    Kyoko Maruyama & Norishige Yoshikawa

  2. Department of Nephrology, National Center for Child Health and Development, Tokyo, Japan

    Kazumoto Iijima

  3. Department of Pediatric Nephrology, Tokyo Metropolitan Children's Hospital, Tokyo, Japan

    Masahiro Ikeda & Masataka Honda

  4. Department of Pediatrics, University of Tokushima School of Medicine, Tokushima, Japan

    Akiko Kitamura

  5. Clinical Biology and Medicine, University of Tokushima School of Medicine, Tokushima, Japan

    Hiroyasu Tsukaguchi

  6. Department of Nephrology, Hara Genito-Urinary Hospital, Kobe, Japan

    Kunihiko Yoshiya

  7. Department of Pediatrics, National Nishi Sapporo Hospital, Sapporo, Japan

    Sakurako Hoshii

  8. Department of Nephrology, Shizuoka Children's Hospital, Shizuoka, Japan

    Naohiro Wada

  9. Department of Pediatrics, Nagoya Daini Red Cross Hospital, Nagoya, Japan

    Osamu Uemura

  10. Department of Pediatric Nephrology, Aichi Children's Health and Medical Center, Aichi, Japan

    Osamu Uemura

  11. Department of Pediatrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan

    Kenichi Satomura

  12. Department of Pediatrics, Wakayama Medical University, Wakayama, Japan

    Norishige Yoshikawa

  13. Department of Nephrology, National Children's Medical Center, National Center for Child Health and Development, 10–1, Okura 2chome, Setagaya-ku, Tokyo 157–8535, Japan

    Kazumoto Iijima

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  1. Kyoko Maruyama
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  2. Kazumoto Iijima
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  3. Masahiro Ikeda
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  4. Akiko Kitamura
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  7. Sakurako Hoshii
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  8. Naohiro Wada
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  9. Osamu Uemura
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  10. Kenichi Satomura
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  11. Masataka Honda
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  12. Norishige Yoshikawa
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Corresponding author

Correspondence to Kazumoto Iijima.

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Maruyama, K., Iijima, K., Ikeda, M. et al. NPHS2 mutations in sporadic steroid-resistant nephrotic syndrome in Japanese children. Pediatr Nephrol 18, 412–416 (2003). https://doi.org/10.1007/s00467-003-1120-6

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  • DOI: https://doi.org/10.1007/s00467-003-1120-6

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