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Report of novel genetic variation in NPHS2 gene associated with idiopathic nephrotic syndrome in South Indian children

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An Erratum to this article was published on 27 July 2016

Abstract

Background

Steroid-resistant nephrotic syndrome (SRNS) is found in 10–20 % of children with idiopathic nephrotic syndrome (INS). In SRNS patients, common histopathological subtypes are Focal segmental glomerulosclerosis (FSGS) (53 %) and minimal change disease (MCD) (27 %). Familial forms of FSGS constitute podocyte diseases with varying severity and age of onset. Podocin gene (NPHS2) mutations cause childhood-onset steroid-resistant FSGS and MCD to adult-onset FSGS. In view of genetic variations and susceptibility to the disease, the present investigation was undertaken to study the pattern of genetic mutation in children from South India.

Methods

Mutation analysis was carried out by direct sequencing of the entire NPHS2 gene (eight exons) using specific primers in 200 INS (100 SRNS and 100 steroid sensitive) children and 100 healthy controls. The allele and genotype frequencies of NPHS2 gene were calculated for both cases and controls as per Hardy–Weinberg equilibrium.

Results

Among the SRNS patients, 18 % revealed both heterozygous and homozygous mutations. Out of 12 mutations, 8 were homozygous and 4 were heterozygous. Interestingly, we found two novel SNPs in exon 4 of NPHS2 gene, which are documented and submitted to dbsnp database (Ref rs12401711 and rs12401708).

Conclusion

Mutational analysis of NPHS2 would be advisable at the start of treatment. The genetic variations detected in the study would serve as the important molecular marker in treating the children’s at early stage, which also enables to detect carriers, prenatal diagnosis and provide genetic counseling to couples at risk.

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Acknowledgments

The authors would like to thank Dr. Mahalingam Vijayakumar and Dr. Prahlad Nageswaran of Department of Pediatric Nephrology, Mehta Children’s Hospital, Chennai, India and Dr. T. Malini, Central Research Facility, Sri Ramachandra University for their valuable support and encouragement.

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Authors and Affiliations

  1. V Clin Bio Labs, Central Research Facility, Sri Ramachandra University, Porur, Chennai, 600 116, India

    Mohanapriya Chinambedu Dhandapani

  2. Department of Human Genetics, Sri Ramachandra University, Porur, Chennai, 600 116, India

    Vettriselvi Venkatesan & Venkatachalam Perumal

  3. Department of Nephrology, Sri Ramachandra University, Porur, Chennai, 600 116, India

    Prabha Sengutavan

  4. Department of Pediatric Nephrology, Mehta Children’s Hospital, Chennai, 600 031, India

    Nammalwar Bollam Rengaswamy & Sudha Ekambaram

  5. Department of Medical Genetics, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, 600 034, India

    Kalpana Gowrishankar

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  1. Mohanapriya Chinambedu Dhandapani
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Correspondence to Venkatachalam Perumal.

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An erratum to this article is available at http://dx.doi.org/10.1007/s10157-016-1259-7.

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Dhandapani, M.C., Venkatesan, V., Rengaswamy, N.B. et al. Report of novel genetic variation in NPHS2 gene associated with idiopathic nephrotic syndrome in South Indian children. Clin Exp Nephrol 21, 127–133 (2017). https://doi.org/10.1007/s10157-016-1237-0

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