Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

De novo mutations of the TRIM8 gene, which codes for a tripartite motif protein, have been identified using whole exome sequencing (WES) in two patients with epileptic encephalopathy (EE), but these reports were not sufficient to conclude that TRIM8 was a novel gene responsible for EE. Here we report four additional patients presenting with EE and de novo truncating mutations of TRIM8 detected by WES, and give further details of the patient previously reported by the Epi4K consortium. Epilepsy of variable severity was diagnosed in children aged 2 months to 3.5 years of age. All patients had developmental delay of variable severity with no or very limited language, often associated with behavioral anomalies and unspecific facial features or MRI brain abnormalities. The phenotypic variability observed in these patients appeared related to the severity of the epilepsy. One patient presented pharmacoresistant EE with regression, recurrent infections and nephrotic syndrome, compatible with the brain and kidney expression of TRIM8. Interestingly, all mutations were located at the highly conserved C-terminus section of TRIM8. This collaborative study confirms that TRIM8 is a novel gene responsible for EE, possibly associated with nephrotic syndrome. This report brings new evidence on the pathogenicity of TRIM8 mutations and highlights the value of data-sharing to delineate the phenotypic characteristics and biological basis of extremely rare disorders.
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PMID:Further delineation of the clinical spectrum of de novo TRIM8 truncating mutations. 3024 34

The faithful inheritance of chromosomes is essential for the propagation of organisms. In eukaryotes, central to this process is the mitotic spindle. Recently, we have identified TRIM8 as a gene aberrantly expressed in gliomas whose expression reduces the clonogenic potential in the patients' glioma cells. TRIM8 encodes an E3 ubiquitin ligase involved in various pathological processes, including hypertrophy, antiviral defense, encephalopathy, and cancer development. To gain insights into the TRIM8 functions, we characterized the TRIM8 interactome in primary mouse embryonic neural stem cells using proteomics. We found that TRIM8 interacts with KIFC1, and KIF11/Eg5, two master regulators of mitotic spindle assembly and cytoskeleton reorganization. By exploring the TRIM8 role in the mitotic spindle machinery, we showed that TRIM8 localizes at the mitotic spindle during mitosis and plays a role in centrosome separation at the beginning of mitosis with a subsequent delay of the mitotic progression and impact on chromosomal stability.
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PMID:TRIM8 interacts with KIF11 and KIFC1 and controls bipolar spindle formation and chromosomal stability. 3190 80

Mutations in the TRIM8 gene have been described in patients with severe developmental delay, intellectual disability and epilepsy. Only six patients have been described to date. All the previous mutations were truncating variants clustered in the C-terminus of the protein. A previous patient with TRIM8-related epileptic encephalopathy was reported to have nephrotic syndrome. Here we describe the clinical, radiological and histological features of an 8-year-old male patient with a TRIM8 mutation who, in contrast to previous patients, had only mild intellectual disability and well-controlled epilepsy. The patient was found to have proteinuria at 2 years of age. Renal biopsy findings were suggestive of focal segmental glomerulosclerosis. His kidney function declined and peritoneal dialysis was started at 5 years of age. He underwent renal transplant at 7 years of age. Trio-based whole genome sequencing identified a novel de novo heterozygous frameshift mutation in TRIM8 (NM_030912.2) c.1198_1220del, p.(Tyr400ArgfsTer2). This patient is further evidence that TRIM8 mutations cause a syndrome with both neurological and renal features. Our findings suggest the spectrum of TRIM8-related disease may be wider than previously thought with the possibility of milder neurodevelopmental problems and/or a more severe, progressive renal phenotype. We highlight the need for proteinuria screening in patients with TRIM8 mutations.
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PMID:Focal segmental glomerulosclerosis and mild intellectual disability in a patient with a novel de novo truncating TRIM8 mutation. 3253 61