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De Novo Truncating Mutation of TRIM8 Causes Early‐Onset Epileptic Encephalopathy
Author(s) -
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
Publication year - 2016
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12157
Subject(s) - exome sequencing , biology , epilepsy , genetics , mutation , encephalopathy , gene duplication , exome , disease gene identification , gene , medicine , neuroscience
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.