De novo variants in RHOBTB2 , an atypical Rho GTPase gene, cause epileptic encephalopathy

• DOI: 10.1002/humu.23550
• Publication Date: 2018-05-16T22:27:24Z
• Authors: Hazrat Belal; Mitsuko Nakashima; Hiroshi Matsumoto; Kenji Yokochi; Mariko Taniguchi‐...; Kazushi Aoto; Mohammed Badrul Amin; Azusa Maruyama; Hiroaki Nagase; Takeshi Mizuguchi; Satoko Miyatake; Noriko Miyake; Kazumoto Iijima; Shigeaki Nonoyama; Naomichi Matsumoto; Hirotomo Saitsu
• Keywords: Adult; Male; rho GTP-Binding Proteins; Epilepsy; Adolescent; Tumor Suppressor Proteins; Infant; 3. Good health; Young Adult; 03 medical and health sciences; 0302 clinical medicine; GTP-Binding Proteins; Child, Preschool; Humans; Female; Child

By whole exome sequencing, we identified three de novo RHOBTB2 variants in patients with epileptic encephalopathies (EEs). Interestingly, all showed acute encephalopathy (febrile status epilepticus), magnetic resonance imaging revealing hemisphere swelling or reduced diffusion various brain regions. encodes Rho-related BTB domain-containing protein 2, an atypical Rho GTPase that is a substrate-specific adaptor itself substrate for the Cullin-3 (CUL3)-based ubiquitin ligase complex. Transient expression experiments Neuro-2a cells revealed mutant was more abundant than wild-type RHOBTB2. Coexpression of CUL3 decreased level but not any mutants, indicating impaired complex-dependent degradation mutants. These data indicate are rare genetic cause EEs, which might be characteristic feature, and precise regulation levels essential normal function.