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Next-Generation Sequencing for Congenital Nephrotic Syndrome: A Multi-Center Cross-Sectional Study from India

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Abstract

Objective

Information on etiology of congenital nephrotic syndrome in non-Caucasian populations is limited. This study aimed to determine the genetic basis of congenital nephrotic syndrome in Indian patients.

Methods

In this observational, cross-sectional study, whole exome sequencing was performed on samples from all children diagnosed with congenital nephrotic syndrome, presenting at centers collaborating in a nationwide registry and biorepository. Analysis was targeted to focus on reported or novel, pathogenic or likely pathogenic variants in 89 genes implicated in etiology of nephrotic syndrome. Sanger sequencing was used to confirm disease-causing variants in patients and allelic segregation of compound heterozygous variants in samples from parents. Inheritance of a shared haplotype was analyzed among ten individuals carrying the most common variant.

Results

During 2017–2019, 34 patients with congenital nephrotic syndrome were screened. Consanguinity and similar illness in siblings were reported in eleven patients each. Homozygous or compound heterozygous, pathogenic or likely pathogenic variants were found in NPHS1 in 24 cases, including two novel variants. One patient each had homozygous pathogenic or likely pathogenic known or novel variant in NPHS2, PLCE1, OSGEP and LAMB2 genes. Patients with OSGEP and LAMB2 mutations had phenotype typical of Galloway Mowat and Pierson syndromes, respectively. Three variants in NPHS1 were common to 16 individuals. One reported variant in exon 19 (c.2600G>A; p.Gly867Asp) appears to share a common founder.

Conclusion

A genetic cause was determined for 82.4% patients with congenital nephrotic syndrome. Variants in NPHS1 are most common in Indian patients and founder mutations might be present.

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Acknowledgments

We thank the following colleagues participating in the NephQuest network who contributed samples and details of their patients: SP Veeturi, Rainbow Children Hospital, Hyderabad; KL Tiewsoh, Postgraduate Institute of Medical Education and Research, Chandigarh; A Mittal, All India Institute of Medical Sciences, Jodhpur; S Krishnamurthy, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry; M Mantan, Maulana Azad Medical College, New Delhi; M Kumar and K Mishra, Chacha Nehru Bal Chikitsalaya, Delhi.

Funding

Department of Biotechnology, Government of India (BT/11030/MED/30/1644/2016).

Author information

Authors and Affiliations

  1. Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology, Delhi, India

    Aditi Joshi, Uzma Shamim, Bharathram Uppilli, Pooja Sharma, Sana Zahra, Shaista Parveen, Aradhana Mathur, Mitali Mukerji & Mohammed Faruq

  2. Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India

    Aditi Sinha, Aakanksha Sharma, Monica Chandan, Prachi Tewari, Priyanka Khandelwal, Pankaj Hari & Arvind Bagga

Authors
  1. Aditi Joshi
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  2. Aditi Sinha
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  3. Aakanksha Sharma
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  14. Mitali Mukerji
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  15. Mohammed Faruq
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  16. Arvind Bagga
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Consortia

NephQuest Consortium

Contributions

All authors contributed to the study conception and design. AJ, AS, AS, MF, AB: material preparation, data collection and analysis were performed; AJ, AS: The first draft of the manuscript was written jointly. All authors commented on the manuscript, and approved the final manuscript.

Corresponding authors

Correspondence to Mohammed Faruq or Arvind Bagga.

Ethics declarations

Ethics committees at CSIR Institute of Genomics and Integrative Biology, Delhi and All India Institute of Medical Sciences, New Delhi; Sanction no. IECPG-616/21.12.2016. RT-33/22.03.2017 and 6/GAP127/CSIR-IGIB/2017

Additional information

Note

Supplementary material related to this study is available with the online version at www.indianpediatrics.net

Competing interest

None stated.

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Joshi, A., Sinha, A., Sharma, A. et al. Next-Generation Sequencing for Congenital Nephrotic Syndrome: A Multi-Center Cross-Sectional Study from India. Indian Pediatr 58, 445–451 (2021). https://doi.org/10.1007/s13312-021-2215-5

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  • DOI: https://doi.org/10.1007/s13312-021-2215-5

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