Abstract:  In adolescents with steroid⁃resistant nephrotic syndrome， the possibility of genetic mutations should be suspected. Mutations in the gene encoding TBC1 domain family member 8B （ TBC1D8B）  can affect podocyte function. We report two young male patients: one presented with nephrotic syndrome accompanied by acute kidney injury （ AKI）， while the other  exhibited  mild  urinary  abnormalities，  AKI，  developmental  delay，  and  epilepsy.  Renal  biopsy  of  both  patients revealed focal  segmental  glomerulosclerosis  combined with tubulointerstitial  injury， both of  whom were  resistant  to  steroid therapy.  Whole⁃exome  sequencing  identified  hemizygous  mutations  in  the  TBC1D8B  gene，  specifically  c. 659T > A  （ p. I220N）  and c.1028T>C （ p.L343P）; both mutations were novel.