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Abstract: SA-PO742

New Mutation in the TNS2 Gene Causes a New Form of Treatable Nephrotic Syndrome

Session Information

Category: Glomerular Diseases

  • 1304 Glomerular Diseases: Podocyte Biology

Authors

  • Martínez Pulleiro, Raquel, Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain
  • Fidalgo diaz, Manuel, Hospital Clinico Universitario de Santiago de Compostela, Servicio de Nefrología, Santiago de Compostela, Spain
  • Carracedo, Angel, Grupo de Medicina Xenómica (GMX), Santiago de Compostela, Spain
  • Rodríguez, Cándido Díaz, Hospital Clinico Universitario de Santiago de Compostela, Servicio de Nefrología, Santiago de Compostela, Spain
  • Garcia-Gonzalez, Miguel A., Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain
Background

Pediatric primary nephrotic syndrome (PNS) is a renal disease characterized by the triad of proteinuria, hypoalbuminemia and edema. Treatment consists of immunosuppressive drugs and corticosteroids and, not in all cases, a satisfactory response is obtained and corticodependence or corticoresistance (SRNS) may develop. Patients may progress to end-stage renal disease (ESRD) and may require dialysis and/or transplantation. In most cases its etiology is unknown, although advances in the molecular genetics of glomerular diseases have shown that single gene defects can affect podocyte structure and function being responsible for one-third or more of all pediatric cases of SRSN. In 2018, Ashraf et al. described a new entity of partially treatment-sensitive SN (pTSNS) and found an underlying genetic cause (six genes involved in the regulation of Rho GTPases in podocytes, including TNS2).

Methods

DNA extraction from a blood sample and mutation detection by NGS sequencing of a panel of glomerular genes. Variant filtering was done based on population and eigen frequencies, quality and functional impact parameters. Interpretation with reference to ACMG criteria.

Results

In our cohort we have a case of pTSNS with multiple recurrences throughout life, persisting into adulthood. All alternative therapies that were tried to limit the high doses of steroids and their respective toxicities were unsuccessful. Genetic diagnosis revealed a previously undescribed homozygous mutation in the TNS2 gene (Asn1262Ile), in a conserved residue, with interpretation of "disease-causing" given by in silico predictors and with a particular phenotype.

Conclusion

The homozygous mutation of the TNS2 gene is responsible for our patient's NS, being the second genetic diagnosis worldwide linking mutations in TNS2 with pathology. Although immunosuppressive treatment achieves disease remission for months, it is not able to prolong it over time. The only way to control relapses is steroids. Knowing the behavior of the SN associated with TNS2 can give the patient a better prognosis of the disease. Regarding genetic diagnosis, there is a need to constantly update the panelized study of genes causing glomerular disease due to the continuous discovery of new genes.