Adult-Onset Focal Segmental Glomerulosclerosis With Steroid-Dependent Nephrotic Syndrome Caused by a Novel TBC1D8B Variant: A Case Report and Literature Review

Focal segmental glomerulosclerosis (FSGS) is a histological lesion with a variety of potential causes, including rare variants of podocyte-related genes. Recently, it has been found that variants in the TBC1D8B gene on the X chromosome can lead to early-onset focal segmental glomerulosclerosis and steroid-resistant nephrotic syndrome by affecting endocytosis and recycling of nephrin. Here, we report a 19-year-old Chinese patient with nephrotic syndrome and normal kidney function. He had a complete remission of nephrotic syndrome after full-dose prednisone and cyclosporine treatment. Unfortunately, a relapse of nephrotic syndrome occurred during prednisone tapering. Focal segmental glomerulosclerosis was proven by a kidney biopsy, and a hemizygous pathogenic variant located in the TBC (Tre-2-Bub2-Cdc16) domain of TBC1D8B was detected by whole-exome sequencing. By comparing our case with reports of other patients with TBC1D8B variants, we suggest possible genotype-phenotype correlations. To our knowledge, this is the first report identifying a pathogenetic variant in the TBC domain of TBC1D8B in an adult-onset focal segmental glomerulosclerosis patient with steroid-dependent NS. With this report, we broaden the clinical and genetic spectrum of X-linked genetic FSGS.

Automated summary

A 19-year-old male Chinese patient with nephrotic syndrome had a complete remission of symptoms after full-dose prednisone and cyclosporine treatment, but experienced a relapse during tapering of prednisone. Kidney biopsy confirmed the presence of focal segmental glomerulosclerosis, and whole-exome sequencing revealed a pathogenic variant in the TBC domain of the TBC1D8B gene. Comparisons with other patients with TBC1D8B variants provided possible genotype-phenotype correlations. This is the first report of a pathogenetic variant in the TBC domain of TBC1D8B in an adult-onset focal segmental glomerulosclerosis patient with steroid-dependent nephrotic syndrome.