De Novo Truncating Mutation of TRIM8 Causes Early‐Onset Epileptic Encephalopathy. (July 2016)

• Record Type: Journal Article
• Authors: Sakai, Yasunari; Fukai, Ryoko; Matsushita, Yuki; Miyake, Noriko; Saitsu, Hirotomo; Akamine, Satoshi; Torio, Michiko; Sasazuki, Momoko; Ishizaki, Yoshito; Sanefuji, Masafumi; Torisu, Hiroyuki; Shaw, Chad A; Matsumoto, Naomichi; Hara, Toshiro
• Is Part Of: Annals of human genetics. Volume 80:Number 4(2016:Jul.)
• Page Start: 235
• Page End: 240
• Publication Date: 2016-07
• Subjects: Epileptic encephalopathy -- developmental delay -- whole‐exome sequencing (WES) -- tripartite motif containing 8 (TRIM8); Human genetics -- Periodicals; 599.935
• DOI: 10.1111/ahg.12157
• Languages: English
• ISSNs: 0003-4800

Abstract

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.