抄録
By whole exome sequencing, we identified three de novo RHOBTB2 variants in three patients with epileptic encephalopathies (EEs). Interestingly, all three patients showed acute encephalopathy (febrile status epilepticus), with magnetic resonance imaging revealing hemisphere swelling or reduced diffusion in various brain regions. RHOBTB2 encodes Rho-related BTB domain-containing protein 2, an atypical Rho GTPase that is a substrate-specific adaptor or itself is a substrate for the Cullin-3 (CUL3)-based ubiquitin ligase complex. Transient expression experiments in Neuro-2a cells revealed that mutant RHOBTB2 was more abundant than wild-type RHOBTB2. Coexpression of CUL3 with RHOBTB2 decreased the level of wild-type RHOBTB2 but not the level of any of the three mutants, indicating impaired CUL3 complex-dependent degradation of the three mutants. These data indicate that RHOBTB2 variants are a rare genetic cause of EEs, in which acute encephalopathy might be a characteristic feature, and that precise regulation of RHOBTB2 levels is essential for normal brain function.
| 元の言語 | English |
|---|---|
| ページ（範囲） | 1070-1075 |
| ページ数 | 6 |
| ジャーナル | Human Mutation |
| 巻 | 39 |
| 発行部数 | 8 |
| DOI | |
| 出版物ステータス | Published - 01-08-2018 |
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All Science Journal Classification (ASJC) codes
- Genetics
- Genetics(clinical)
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De novo variants in RHOBTB2, an atypical Rho GTPase gene, cause epileptic encephalopathy. / Belal, Hazrat; Nakashima, Mitsuko; Matsumoto, Hiroshi; Yokochi, Kenji; Ikeda, Mariko; Aoto, Kazushi; Amin, Mohammed Badrul; Maruyama, Azusa; Nagase, Hiroaki; Mizuguchi, Takeshi; Miyatake, Satoko; Miyake, Noriko; Iijima, Kazumoto; Nonoyama, Shigeaki; Matsumoto, Naomichi; Saitsu, Hirotomo.
：: Human Mutation, 巻 39, 番号 8, 01.08.2018, p. 1070-1075.研究成果: Article
TY - JOUR
T1 - De novo variants in RHOBTB2, an atypical Rho GTPase gene, cause epileptic encephalopathy
AU - Belal, Hazrat
AU - Nakashima, Mitsuko
AU - Matsumoto, Hiroshi
AU - Yokochi, Kenji
AU - Ikeda, Mariko
AU - Aoto, Kazushi
AU - Amin, Mohammed Badrul
AU - Maruyama, Azusa
AU - Nagase, Hiroaki
AU - Mizuguchi, Takeshi
AU - Miyatake, Satoko
AU - Miyake, Noriko
AU - Iijima, Kazumoto
AU - Nonoyama, Shigeaki
AU - Matsumoto, Naomichi
AU - Saitsu, Hirotomo
PY - 2018/8/1
Y1 - 2018/8/1
N2 - By whole exome sequencing, we identified three de novo RHOBTB2 variants in three patients with epileptic encephalopathies (EEs). Interestingly, all three patients showed acute encephalopathy (febrile status epilepticus), with magnetic resonance imaging revealing hemisphere swelling or reduced diffusion in various brain regions. RHOBTB2 encodes Rho-related BTB domain-containing protein 2, an atypical Rho GTPase that is a substrate-specific adaptor or itself is a substrate for the Cullin-3 (CUL3)-based ubiquitin ligase complex. Transient expression experiments in Neuro-2a cells revealed that mutant RHOBTB2 was more abundant than wild-type RHOBTB2. Coexpression of CUL3 with RHOBTB2 decreased the level of wild-type RHOBTB2 but not the level of any of the three mutants, indicating impaired CUL3 complex-dependent degradation of the three mutants. These data indicate that RHOBTB2 variants are a rare genetic cause of EEs, in which acute encephalopathy might be a characteristic feature, and that precise regulation of RHOBTB2 levels is essential for normal brain function.
AB - By whole exome sequencing, we identified three de novo RHOBTB2 variants in three patients with epileptic encephalopathies (EEs). Interestingly, all three patients showed acute encephalopathy (febrile status epilepticus), with magnetic resonance imaging revealing hemisphere swelling or reduced diffusion in various brain regions. RHOBTB2 encodes Rho-related BTB domain-containing protein 2, an atypical Rho GTPase that is a substrate-specific adaptor or itself is a substrate for the Cullin-3 (CUL3)-based ubiquitin ligase complex. Transient expression experiments in Neuro-2a cells revealed that mutant RHOBTB2 was more abundant than wild-type RHOBTB2. Coexpression of CUL3 with RHOBTB2 decreased the level of wild-type RHOBTB2 but not the level of any of the three mutants, indicating impaired CUL3 complex-dependent degradation of the three mutants. These data indicate that RHOBTB2 variants are a rare genetic cause of EEs, in which acute encephalopathy might be a characteristic feature, and that precise regulation of RHOBTB2 levels is essential for normal brain function.
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U2 - 10.1002/humu.23550
DO - 10.1002/humu.23550
M3 - Article
AN - SCOPUS:85049862116
VL - 39
SP - 1070
EP - 1075
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 8
ER -