[SP6-3D-3] TRIM8 is a new gene associated with early-onset epileptic encephalopathy
Background: Early-onset epileptic encephalopathy (EOEE) is a heterogeneous group of neurodevelopmental disorders characterized by infantile-onset intractable epilepsy and severe developmental delay. Hundreds of mutations have been associated with EOEE. Little is known, however, about the clinical features of individuals with rare variants and their pathogenic mechanisms.
Case report and Results: We present a 10-year-old boy with severe developmental delay. He started experiencing recurrent focal seizures at 2 months of age. Serial electroencephalograms detected epileptiform discharges from the left hemisphere. Array-comparative genome hybridization and whole-exome sequencing were performed in search for causal genetic variations. This case had paternally inherited, 0.2-Mb duplication at chromosome 22q11.22, encompassing the TOP3B locus. The whole-exome sequencing identified a de novo truncating mutation of tripartite motif containing 8 (TRIM8). We found that the murine homolog of TRIM8 was expressed in the postnatal brain of mice, and that its expression signals were closely located at the postsynaptic marker, Psd95. RNA-targeted immunoprecipitation assays for mouse brain extracts showed that Top3b-bound ribonucleoprotein complex contained Trim8 mRNA.
Conclusion: We herein presented the clinical profiles of a case with EOEE caused by a de novo truncating mutation of TRIM8. Experimental data suggested the functional roles of TRIM8 in the postnatal development of human brain.
Case report and Results: We present a 10-year-old boy with severe developmental delay. He started experiencing recurrent focal seizures at 2 months of age. Serial electroencephalograms detected epileptiform discharges from the left hemisphere. Array-comparative genome hybridization and whole-exome sequencing were performed in search for causal genetic variations. This case had paternally inherited, 0.2-Mb duplication at chromosome 22q11.22, encompassing the TOP3B locus. The whole-exome sequencing identified a de novo truncating mutation of tripartite motif containing 8 (TRIM8). We found that the murine homolog of TRIM8 was expressed in the postnatal brain of mice, and that its expression signals were closely located at the postsynaptic marker, Psd95. RNA-targeted immunoprecipitation assays for mouse brain extracts showed that Top3b-bound ribonucleoprotein complex contained Trim8 mRNA.
Conclusion: We herein presented the clinical profiles of a case with EOEE caused by a de novo truncating mutation of TRIM8. Experimental data suggested the functional roles of TRIM8 in the postnatal development of human brain.