1. Association of a de novo nonsense mutation of the TRIM8 gene with childhood-onset focal segmental glomerulosclerosis
- Author
-
Moe Takeda, Arthur Partikian, Richard N. Fine, Lawrence M. Opas, Shoji Yano, and Mikako Warren
- Subjects
Nephrology ,Male ,medicine.medical_specialty ,Drug Resistant Epilepsy ,Nonsense mutation ,030232 urology & nephrology ,Nerve Tissue Proteins ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Focal segmental glomerulosclerosis ,Suppressor of Cytokine Signaling 1 Protein ,Internal medicine ,medicine ,Humans ,Child ,Gene ,Mutation ,medicine.diagnostic_test ,urogenital system ,business.industry ,Suppressor of cytokine signaling 1 ,Glomerulosclerosis, Focal Segmental ,Podocytes ,High-Throughput Nucleotide Sequencing ,medicine.disease ,Codon, Nonsense ,Pediatrics, Perinatology and Child Health ,Cancer research ,Renal biopsy ,business ,Carrier Proteins ,Nephrotic syndrome - Abstract
Focal segmental glomerulosclerosis (FSGS) is an etiologically heterogeneous disorder. Genetic FSGS may be either limited to the kidney or part of a genetic syndrome with other systemic involvement. At least 21 and 34 genes have been reported for renal-limited and syndromic FSGS, respectively. The TRIM8 gene encodes a tripartite motif protein, which is an E3 ubiquitin-protein ligase that promotes proteasomal degradation of the suppressor of cytokine signaling 1 (SOCS1) and participates in the activation of interferon-gamma signaling. The TRIM8 gene is expressed in various tissues including the kidney and the central nervous system (CNS). An association between a mutation in the TRIM8 gene and childhood-onset FSGS has not been well established. We describe an 8-year-old Hispanic male with infantile onset motor and developmental delay, seizures, and proteinuria secondary to FSGS. Next generation sequencing revealed a heterozygous de novo pathogenic variant in the TRIM8 gene (C1380T>A, p.Tyr460*). Immunohistochemical staining using anti-TRIM8 and anti-SOCS1 antibodies showed no significant TRIM8 expression and strong expression of SOCS1 in the renal biopsy tissue. De novo truncating mutations of TRIM8 have been previously reported in childhood-onset epileptic encephalopathy. A molecular analysis of TRIM8 should be considered in children with FSGS and clinical abnormalities of the central nervous system.
- Published
- 2019