De Novo Truncating Mutation of TRIM8 Causes Early-Onset Epileptic Encephalopathy

Yasunari Sakai, Ryoko Fukai, Yuki Matsushita, Noriko Miyake, Hirotomo Saitsu, Satoshi Akamine, Michiko Torio, Momoko Sasazuki, Yoshito Ishizaki, Masafumi Sanefuji, Hiroyuki Torisu, Chad A. Shaw, Naomichi Matsumoto, Toshiro Hara

Research output: Contribution to journalArticle

3 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)235-240
Number of pages6
JournalAnnals of Human Genetics
Volume80
Issue number4
DOIs
Publication statusPublished - Jul 1 2016

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Brain Diseases
Mutation
Exome
Chromosome Duplication
Genes
Comparative Genomic Hybridization
Brain
Human Development
Fluorescent Antibody Technique
Electroencephalography
Seizures

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Sakai, Y., Fukai, R., Matsushita, Y., Miyake, N., Saitsu, H., Akamine, S., ... Hara, T. (2016). De Novo Truncating Mutation of TRIM8 Causes Early-Onset Epileptic Encephalopathy. Annals of Human Genetics, 80(4), 235-240. https://doi.org/10.1111/ahg.12157

De Novo Truncating Mutation of TRIM8 Causes Early-Onset Epileptic Encephalopathy. / 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.

In: Annals of Human Genetics, Vol. 80, No. 4, 01.07.2016, p. 235-240.

Research output: Contribution to journalArticle

Sakai, Y, Fukai, R, Matsushita, Y, Miyake, N, Saitsu, H, Akamine, S, Torio, M, Sasazuki, M, Ishizaki, Y, Sanefuji, M, Torisu, H, Shaw, CA, Matsumoto, N & Hara, T 2016, 'De Novo Truncating Mutation of TRIM8 Causes Early-Onset Epileptic Encephalopathy', Annals of Human Genetics, vol. 80, no. 4, pp. 235-240. https://doi.org/10.1111/ahg.12157
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. / De Novo Truncating Mutation of TRIM8 Causes Early-Onset Epileptic Encephalopathy. In: Annals of Human Genetics. 2016 ; Vol. 80, No. 4. pp. 235-240.
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AU - Saitsu, Hirotomo

AU - Akamine, Satoshi

AU - Torio, Michiko

AU - Sasazuki, Momoko

AU - Ishizaki, Yoshito

AU - Sanefuji, Masafumi

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AU - Shaw, Chad A.

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