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FB2026_01
,
released March 12, 2026
This report describes developmental and epileptic encephalopathy 64 (DEE64), previously called epileptic encephalopathy, early infantile, 64 (EIEE64); DEE64 exhibits autosomal dominant inheritance. The human gene implicated in this disease is RHOBTB2, a small highly conserved Rho GTPase. There is a single orthologous gene in Drosophila, RhoBTB, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated. Dmel\RhoBTB is also orthologous to the human RHOBTB1 gene.
A UAS construct of the wild-type human Hsap\RHOBTB2 gene has been introduced into flies, but has not been characterized.
Pan-neuronal overexpression of Dmel\RhoBTB results in a bang-sensitive (seizure susceptibility) phenotype; pan-neuronal knockdown of RhoBTB effected by RNAi results in no or milder bang-sensitivity. Overexpression of RhoBTB in several tissues (pan-neuronal, motoneurons, muscle, and glia) results in marked locomotor impairment, whereas RNAi-mediated knockdown causes no significant differences from the respective controls. A small number of genetic and physical interactions have been described for Dmel\RhoBTB; see below and in the RhoBTB gene report.
[updated Feb. 2021 by FlyBase; FBrf0222196]
[DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 64; DEE64](https://omim.org/entry/618004)
[RHO-RELATED BTB DOMAIN-CONTAINING PROTEIN 2; RHOBTB2](https://omim.org/entry/607352)
Early infantile epileptic encephalopathy-64 is a neurodevelopmental disorder characterized by onset of seizures usually in the first year of life and associated with intellectual disability, poor motor development, and poor or absent speech. Additional features include hypotonia, abnormal movements, and nonspecific dysmorphic features. The severity is variable: some patients are unable to speak, walk, or interact with others as late as the teenage years, whereas others may have some comprehension (summary by Straub et al., 2018; pubmed:29276004). [from MIM:618004; 2018.07.03]
Early infantile epileptic encephalopathy-64 (EIEE64) is caused by heterozygous mutation in the RHOBTB2 gene. [from MIM:618004; 2018.07.03]
RHOBTB2 encodes a small highly conserved Rho GTPase that interacts with the cullin-3 protein, a ubiquitin E3 ligase necessary for mitotic cell division. RHOBTB2 is a candidate tumor suppressor. [from Gene Cards, RHOBTB2; 2018.07.05]
Many to one: 2 human to 1 Drosophila; the second human gene is RHOBTB1.
High-scoring ortholog of human RHOBTB1 and RHOBTB2 (1 Drosophila to 2 human). Dmel\RhoBTB shares 38-42% identity and 52-57% similarity with the human genes.