A novel de novo truncating TRIM8 variant associated with childhood-onset focal segmental glomerulosclerosis without epileptic encephalopathy: a case report

Abstract

Abstract Background Heterozygous truncating variants in the Tripartite motif containing 8 (TRIM8) gene have been reported to cause epileptic encephalopathy, both with and without proteinuria. A recent study showed a lack of TRIM8 protein expression, with suppressor of cytokine signaling 1 (SOCS1) overexpression, in podocytes and tubules from a patient with a TRIM8 variant, who presented with epileptic encephalopathy and focal segmental glomerulosclerosis (FSGS). To date, no patients with TRIM8 variants who presented with nephrotic syndrome but without neurological manifestations have been described. Case presentation An 8-year-old girl presented with nephrotic syndrome, without epilepsy or developmental delay. Her kidney biopsy specimens showed FSGS and cystic dilatations of the distal tubules. Whole-exome sequencing identified a novel de novo heterozygous variant in the C-terminal encoding portion of TRIM8 (c.1461C > A), resulting in a premature stop codon (p.Tyr487*). Reverse transcription-polymerase chain reaction using peripheral blood mononuclear cells identified the mRNA sequence of the mutant allele, which confirmed an escape from nonsense-mediated mRNA decay. Immunofluorescence studies showed a lack of TRIM8 expression in glomerular and tubular cells and cystic dilatation of distal tubules. Immunohistochemical studies showed overexpression of SOCS1 in glomerular and tubular cells. Conclusions We reported a patient with FSGS, associated with a de novo heterozygous TRIM8 variant, without any neurological manifestations. Our results expanded the clinical phenotypic spectrum of TRIM8 variants.