title: De Novo Truncating Mutation of TRIM8 Causes Early-Onset Epileptic Encephalopathy.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Department of Human Genetics, Yokohama City University School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Fukai
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsushita
authors.affiliation: Department of Human Genetics, Yokohama City University School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Human Genetics, Yokohama City University School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Akamine
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Torio
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Sasazuki
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Ishizaki
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Sanefuji
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.|Section of Pediatrics, Department of Medicine, Fukuoka Dental College, Fukuoka, 814-0193, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Torisu
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 77030, TX, USA.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Shaw
authors.affiliation: Department of Human Genetics, Yokohama City University School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000235:genetics; D059472:Exome; D015870:Gene Expression; D006801:Humans; D007223:Infant; D008297:Male; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D013036:Spasms, Infantile / Q000175:diagnosis* / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D018389:Codon, Nonsense; D009419:Nerve Tissue Proteins; C418604:TRIM8 protein, human
keywords: Epileptic encephalopathy; developmental delay; tripartite motif containing 8 (TRIM8); whole-exome sequencing (WES)