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ORIGINAL RESEARCH article
Front. Neurol.
Sec. Pediatric Neurology
Volume 15 - 2024 |
doi: 10.3389/fneur.2024.1410187
Variants loci and phenotype correlation of TRIM8-related neuro-renal syndrome: Three cases reports and literature review
Provisionally accepted- 1 Department of Pediatrics, Peking University People's Hospital, Beijing, Beijing Municipality, China
- 2 Peking University People's Hospital, Beijing, China
TRIM8-related neuro-renal syndrome (NRS), caused by pathogenic variants of the TRIM8 gene, is characterized by epilepsy, developmental delay (DD) and renal disorders. The severity of the neurological effects as well as the presence of renal disorders is variable among patients. Here, we report three additional patients with clinical features compatible with NRS, exploring clinical variability and the relationship between genotypic changes and phenotypic outcomes. Demographic and clinical data were collected from these patients. Variants were verified through triobased whole-exome sequencing or Sanger sequencing. Two de novo TRIM8 truncating variants in three NRS patients were identified in our study, including c.1327_c.1328delCCinsTG (p. Arg443*) and c.1375C > T (p. Gln459*). Our three patients all exhibited drug-resistant epilepsy and early-onset DD, and two of whom developed electrical status epilepticus during sleep (ESES). Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia in one patient and normal in the other two. All three patients demonstrated nephrotic range proteinuria (NRP) or nephrotic syndrome (NS) with normal renal function during follow-up. Furthermore, we reviewed published articles on TRIM8 variants and identified 9 studies. There was a total of 27 patients with TRIM8-related NRS have been identified to date. The most common clinical features are renal diseases (89%), DD (89%), followed by epilepsy (78%). 67% of patients eventually progressed to end-stage renal disease (ESRD). Focal seizure was the most frequent seizure type (57%). 52% of patients presented drug-resistant epilepsy. 64% of patients exhibited non-specific brain MRI abnormalities. Brain atrophy was the most common change (50%). Two patients with TRIM8 variants closer to the N-terminal had neurological diseases without renal damage. Five patients with TRIM8 variants closer to the C-terminal had no severe neurological diseases. Seven patients had Gln459* variant which is the most common variant (7/27, 25.9%). The severity of the renal and neurological damage of the seven patients was variable. Further research is needed to explore the relationship between genotype and phenotype of TRIM8 variants.
Keywords: TRIM8, neuro-renal syndrome, Epilepsy, developmental delay, Nephrotic Syndrome, Proteinuria
Received: 31 Mar 2024; Accepted: 04 Sep 2024.
Copyright: © 2024 Lv, Niu, Xu, Qin and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jiong Qin, Department of Pediatrics, Peking University People's Hospital, Beijing, 100044, Beijing Municipality, China
Zhixian Yang, Department of Pediatrics, Peking University People's Hospital, Beijing, 100044, Beijing Municipality, China
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