De Novo Truncating Mutation of TRIM8 Causes Early‐Onset Epileptic Encephalopathy
Summary Background Early‐onset epileptic encephalopathy (EOEE) is a heterogeneous group of neurodevelopmental disorders characterised by infantile‐onset intractable epilepsy and unfavourable developmental outcomes. Hundreds of mutations have been reported to cause EOEE; however, little is known abou...
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Published in | Annals of human genetics Vol. 80; no. 4; pp. 235 - 240 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Wiley Subscription Services, Inc
01.07.2016
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Subjects | |
Online Access | Get full text |
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Summary: | Summary
Background
Early‐onset epileptic encephalopathy (EOEE) is a heterogeneous group of neurodevelopmental disorders characterised by infantile‐onset intractable epilepsy and unfavourable developmental outcomes. Hundreds of mutations have been reported to cause EOEE; however, little is known about the clinical features of individuals with rare variants.
Case report and methods
We present a 10‐year‐old boy with severe developmental delay. He started experiencing recurrent focal seizures at 2 months old. Serial electroencephalograms persistently detected epileptiform discharges from the left hemisphere. Whole‐exome sequencing and array‐comparative genome hybridization were performed to search for de novo variations. Two‐week‐old C57Bl/6 mice were used for immunofluorescence studies.
Results
This case had a paternally inherited, 0.2‐Mb duplication at chromosome 22q11.22. The whole‐exome sequencing identified a de novo truncating mutation of tripartite motif containing 8 (TRIM8) (NM_030912:c.1099_1100insG:p.C367fs), one of the epileptic encephalopathy‐associated genes. We verified that the murine homologues of these genes are expressed in the postnatal mouse brain.
Conclusion
This is the second case of EOEE caused by a de novo truncating mutation of TRIM8. Further studies are required to determine the functional roles of TRIM8 in the postnatal development of the human brain and its functional relationships with other EOEE‐associated genes. |
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Bibliography: | Present address: Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu 431‐3192, Japan These authors contributed equally to this work. Present address: Fukuoka Children's Hospital, Fukuoka 813‐0017, Japan ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0003-4800 1469-1809 |
DOI: | 10.1111/ahg.12157 |