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Genetic Testing in Pediatric Kidney Disease


The advent of next gene sequencing technology has led to the publication of a profusion of papers on monogenic contributions to pediatric kidney disorders. It started with the discovery of mutations in the podocin gene in steroid resistant nephrotic syndrome (SRNS). It is realized now that genetic disorders contribute to about 30% of chronic renal diseases in children, and significantly to many other kidney disorders. This paper covers briefly the new genetic technologies, the benefits of genetic testing, and the indication for genetic testing in various kidney disorders. It covers SRNS, congenital anomalies of the kidney, cystic kidney disease, tubulopathies, nephronophthisis, Fabry disease, Alport and Lowe syndrome. Atypical hemolytic uremic syndrome, renal tubular acidosis and nephrolithiasis are also covered briefly. It is hoped that this paper will encourage the pediatricians to investigate monogenic disorders of the kidney as it helps in their proper classification, informs prognosis, suggests specific treatment and aids in genetic and reproductive counseling.

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  1. 1.

    Armstrong ME, Thomas CP. Diagnosis of monogenic chronic kidney diseases. Curr Opin Nephrol Hypertens. 2019;28:183–94.

  2. 2.

    Connaughton DM, Hildebrandt F. Personalized medicine in chronic kidney disease by detection of monogenic mutations. Nephrol Dial Transplant. 2019. https://doi.org/10.1093/ndt/gfz028.

  3. 3.

    Gulati A, Somlo S. Whole exome sequencing: a state-of-the-art approach for defining (and exploring!) genetic landscapes in pediatric nephrology. Pediatr Nephrol. 2018;33:745–61.

  4. 4.

    Tullus K, Webb H, Bagga A. Management of steroid-resistant nephrotic syndrome in children and adolescents. Lancet Child Adolesc Health. 2018;2:880–90.

  5. 5.

    Sadowski CE, Lovric S, Ashraf S, et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2015;26:1279–89.

  6. 6.

    Ramanathan AS, Vijayan M, Rajagopal S, Rajendiran P, Senguttuvan P. WT1 and NPHS2 gene mutation analysis and clinical management of steroid-resistant nephrotic syndrome. Mol Cell Biochem. 2017;426:177–81.

  7. 7.

    Mishra OP, Singh AK, Abhinay A, Narayan G, Prasad R, Batra VV. WT1 mutations in steroid-resistant idiopathic nephrotic syndrome. Saudi J Kidney Dis Transpl. 2016;27:417–8.

  8. 8.

    Jaffer A, Unnisa W, Raju DS, Jahan P. NPHS2 mutation analysis and primary nephrotic syndrome in southern Indians. Nephrology (Carlton). 2014;19:398–403.

  9. 9.

    Lovric S, Ashraf S, Tan W, Hildebrandt F. Genetic testing in steroid-resistant nephrotic syndrome: when and how? Nephrol Dial Transplant. 2016;31:1802–13.

  10. 10.

    Yulia A, Winyard P. Management of antenatally detected kidney malformations. Early Hum Dev. 2018;126:38–46.

  11. 11.

    van der Ven AT, Vivante A, Hildebrandt F. Novel insights into the pathogenesis of monogenic congenital anomalies of the kidney and urinary tract. J Am Soc Nephrol. 2018;29:36–50.

  12. 12.

    De Tomasi L, David P, Humbert C, et al. Mutations in GREB1L cause bilateral kidney agenesis in humans and mice. Am J Hum Genet. 2017;101:803–14.

  13. 13.

    van der Ven AT, Connaughton DM, Ityel H, Mann N, Nakayama M, Chen J. Whole-exome sequencing identifies causative mutations in families with congenital anomalies of the kidney and urinary tract. J Am Soc Nephrol. 2018;29:2348–61.

  14. 14.

    Germain DP, Fouilhoux A, Decramer S, et al. Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients. Clin Genet. 2019. https://doi.org/10.1111/cge.13546.

  15. 15.

    Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. NEJM. 2011;364:1533–43.

  16. 16.

    Chandrasekar SP, Namboothiri S, Sen P, Sarangapani S. Screening for mutation hotspots in Bardet-Biedl syndrome patients from India. Indian J Med Res. 2018;147:177–82.

  17. 17.

    Harris PC, Torres VE. Polycystic kidney disease, autosomal dominant. 2002 Jan 10 [updated 2018 Jul 19]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1246/.

  18. 18.

    Arora V, Bijarnia-Mahay S, Tiwari V, et al. Co-inheritance of pathogenic variants in PKD1 and PKD2 genes presenting as severe antenatal phenotype of autosomal dominant polycystic kidney disease. Eur J Med Genet. 2019;23. https://doi.org/10.1016/j.ejmg.2019.103734.

  19. 19.

    Pandita S, Ramachandran V, Balakrishnan P, et al. Identification of Pkd1 and Pkd2 gene variants in a cohort of 125 Asian Indian patients of ADPKD. J Hum Genet. 2019;64:409–19.

  20. 20.

    Sweeney WE, Avner ED. Polycystic kidney disease, autosomal recessive. 2001 Jul 19 [updated 2019 Feb 14]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1326/.

  21. 21.

    Stokman M, Lilien M, Knoers N. Nephronophthisis. 2016 Jun 23. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2019. Available at: https://www.ncbi.nlm.nih.gov/books/NBK368475/.

  22. 22.

    Kashtan CE, Ding J, Garosi G, et al. Alport syndrome: a unified classification of genetic disorders of collagen IV α345: a position paper of the Alport syndrome classification working group. Kidney Int. 2018;93:1045–51.

  23. 23.

    Jais JP, Knebelmann B, Giatras I, et al. X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a “European Community Alport Syndrome Concerted Action” study. J Am Soc Nephrol. 2003;14:2603–10.

  24. 24.

    Lewis RA, Nussbaum RL, Brewer ED. Lowe syndrome. 2001 Jul 24 [updated 2019 Apr 18]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [internet]. Seattle (WA): University of Washington, Seattle; 1993–2019

  25. 25.

    Fulchiero R, Seo-Mayer P. Bartter syndrome and Gitelman syndrome. Pediatr Clin N Am. 2019;66:121–34.

  26. 26.

    Loirat C, Fakhouri F, Ariceta G, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016;31:15–39.

  27. 27.

    Thergaonkar RW, Narang A, Gurjar BS, et al. Targeted exome sequencing in anti-factor H antibody negative HUS reveals multiple variations. Clin Exp Nephrol. 2018;22:653–60.

  28. 28.

    Noris M, Bresin E, Mele C, Remuzzi G. Genetic atypical hemolytic-uremic syndrome. 2007 Nov 16 [updated 2016 Jun 9]. In: Adam MP, Ardinger HH, Pagon RA, et al, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1367/.

  29. 29.

    Mattoo TK. Etiology and clinical manifestations of renal tubular acidosis in infants and children. In: Stapleton FB, Kim MS, editors. UpToDate [Internet]. UpToDate Inc; 2019 [cited 2019 Nov 10].

  30. 30.

    Braun DA, Lawson JA, Gee MJ, et al. Prevalence of monogenic causes in pediatric patients with nephrolithiasis or nephrocalcinosis. Clin J Am Soc Nephrol. 2016;11:664–72.

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Each author wrote 1/3rd of the paper, the part pertaining to their area of expertise. The guarantor of the paper is Dr. Sunita Bijarnia, Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi.

Correspondence to Ishwar Chander Verma.

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Arora, V., Anand, K. & Chander Verma, I. Genetic Testing in Pediatric Kidney Disease. Indian J Pediatr (2020). https://doi.org/10.1007/s12098-020-03198-y

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  • Genetic testing
  • Genetic disorders
  • Pediatric kidney disease
  • SRNS
  • Tubulopathies
  • Atypical hemolytic uremic syndrome
  • RTA
  • Alport syndrome
  • Next gene sequencing