2016年6月
De Novo Truncating Mutation of TRIM8 Causes Early-Onset Epileptic Encephalopathy
ANNALS OF HUMAN GENETICS
- 巻
- 80
- 号
- 4
- 開始ページ
- 235
- 終了ページ
- 240
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/ahg.12157
- 出版者・発行元
- WILEY-BLACKWELL
BackgroundEarly-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 methodsWe 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.
ResultsThis 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.
ConclusionThis 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.
Case report and methodsWe 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.
ResultsThis 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.
ConclusionThis 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.
- リンク情報
- ID情報
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- DOI : 10.1111/ahg.12157
- ISSN : 0003-4800
- eISSN : 1469-1809
- PubMed ID : 27346735
- Web of Science ID : WOS:000379682000005