Mutational landscape of TRPC6, WT1, LMX1B, APOL1, PTPRO, PMM2, LAMB2 and WT1 genes associated with Steroid resistant nephrotic syndrome

Mol Biol Rep. 2021 Nov;48(11):7193-7201. doi: 10.1007/s11033-021-06711-4. Epub 2021 Sep 21.


Background: Nephrotic syndrome appears as a group of symptoms like proteinuria, edema and hyperlipidemia. Identification of monogenic forms revealed the physiology and pathogenesis of the SRNS.

Methods and results: We performed Illumina panel sequencing of seven genes in 90 Indian patients to determine the role of these genetic mutations in nephrotic syndrome prognosis. Samtool was used for variants calling, and SnpEff and Snpsift did variants annotation. Clinical significance and variant classification were performed by the ClinVar database. In SSNS and SRNS patients, we found 0.78% pathogenic and 3.41% likely pathogenic mutations. Pathogenic mutations were found in LAMB2, LMX1B and WT1 genes, while likely pathogenic mutations were found in (6/13) LAMB2, (2/13) LMX1B, (2/13) TRPC6, (2/13) PTPRO and (1/13) PMM2 genes. Approximately 46% likely pathogenic mutations were contributed to the LAMB2 gene in SSNS and SRNS patients. We also detect 30 VUS (variants of uncertain significance), which were found (17/30) pathogenic and (13/30) likely pathogenic by different prediction tools.

Conclusions: Multigene panels were used for genetic screening of heterogeneous disorders like nephrotic syndrome in the Indian population. We found pathogenic, likely pathogenic and certain VUS, which were responsible for the pathogenesis of the disease. Therefore, mutational analysis of SSNS and SRNS is necessary to avoid adverse effects of corticosteroids, modify the intensity of immunosuppressing agents, and prevent the disease's progression.

Keywords: Illumina panel sequencing; Indian patients; Steroid resistant nephrotic syndrome (SRNS); Steroid sensitive nephrotic syndrome (SSNS).

MeSH terms

  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Genes, Wilms Tumor
  • Genetic Predisposition to Disease*
  • Humans
  • LIM-Homeodomain Proteins / genetics
  • Laminin / genetics
  • Male
  • Mutation*
  • Nephrotic Syndrome / genetics*
  • Phosphotransferases (Phosphomutases) / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / genetics
  • TRPC6 Cation Channel / genetics
  • Transcription Factors / genetics


  • LIM homeobox transcription factor 1 beta
  • LIM-Homeodomain Proteins
  • Laminin
  • TRPC6 Cation Channel
  • TRPC6 protein, human
  • Transcription Factors
  • laminin beta2
  • PTPRO protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3
  • Phosphotransferases (Phosphomutases)
  • phosphomannomutase 2, human