RHOBTB2 p.Arg511Trp Mutation in Early Infantile Epileptic Encephalopathy-64: Review and Case Report

Abstract

Early infantile epileptic encephalopathy-64 (EIEE 64), also called RHOBTB2-related developmental and epileptic encephalopathy (DEE), is caused by heterozygous pathogenic variants (EIEE 64; MIM#618004) in the Rho-related BTB domain-containing protein 2 (RHOBTB2) gene. To date, only 13 cases with RHOBTB2-related DEE have been reported. We add to the literature the 14th case of EIEE 64, identified by whole exome sequencing, caused by a heterozygous pathogenic variant in RHOBTB2 (c.1531C > T), p.Arg511Trp. This additional case supports the main features of RHOBTB2-related DEE: infantile-onset seizures, severe intellectual disability, impaired motor functions, postnatal microcephaly, recurrent status epilepticus, and hemiparesis after seizures.

Keywords

RHOBTB2 - early infantile epileptic encephalopathy-64 - developmental and epileptic encephalopathy

Publikationsverlauf

Eingereicht: 30. Juni 2020

Angenommen: 23. November 2020

Artikel online veröffentlicht:
02. Februar 2021

• References

• 1 Scheffer IE, Berkovic S, Capovilla G. et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58 (04) 512-521
• 2 Scheffer IE, Liao J. Deciphering the concepts behind “epileptic encephalopathy” and “developmental and epileptic encephalopathy.”. Eur J Paediatr Neurol 2020; 24: 11-14
• 3 McTague A, Howell KB, Cross JH, Kurian MA, Scheffer IE. The genetic landscape of the epileptic encephalopathies of infancy and childhood. Lancet Neurol 2016; 15 (03) 304-316
• 4 Happ HC, Carvill GLA. A 2020 view on the genetics of developmental and epileptic encephalopathies. Epilepsy Curr 2020; 20 (02) 90-96
• 5 Hamaguchi M, Meth JL, von Klitzing C. et al. DBC2, a candidate for a tumor suppressor gene involved in breast cancer. Proc Natl Acad Sci USA 2002; 99 (21) 13647-13652
• 6 Straub J, Konrad EDH, Grüner J. et al; Deciphering Developmental Disorders Study. Missense variants in RHOBTB2 cause a developmental and epileptic encephalopathy in humans, and altered levels cause neurological defects in Drosophila . Am J Hum Genet 2018; 102 (01) 44-57
• 7 Belal H, Nakashima M, Matsumoto H. et al. De novo variants in RHOBTB2, an atypical Rho GTPase gene, cause epileptic encephalopathy. Hum Mutat 2018; 39 (08) 1070-1075
• 8 Knijnenburg ACS, Nicolai J, Bok LA. et al. Acute encephalopathy after head trauma in a patient with a RHOBTB2 mutation. Neurol Genet 2020; 6 (03) e418
• 9 Choi YM, Kim KB, Lee JH. et al. DBC2/RhoBTB2 functions as a tumor suppressor protein via musashi-2 ubiquitination in breast cancer. Oncogene 2017; 36 (20) 2802-2812
• 10 Wang CJ, Yang D, Luo YW. RhoBTB2 (DBC2) functions as a multifunctional tumor suppressor in thyroid cancer cells via mitochondrial apoptotic pathway. Int J Clin Exp Med 2015; 8 (04) 5954-5958
• 11 Mao H, Zhang L, Yang Y. et al. RhoBTB2 (DBC2) functions as tumor suppressor via inhibiting proliferation, preventing colony formation and inducing apoptosis in breast cancer cells. Gene 2011; 486 (1-2): 74-80
• 12 Gonsales MC, Montenegro MA, Soler CV, Coan AC, Guerreiro MM, Lopes-Cendes I. Recent developments in the genetics of childhood epileptic encephalopathies: impact in clinical practice. Arq Neuropsiquiatr 2015; 73 (11) 946-958
• 13 Allen NM, Conroy J, Shahwan A. et al. Unexplained early onset epileptic encephalopathy: exome screening and phenotype expansion. Epilepsia 2016; 57 (01) e12-e17
• 14 Palmer EE, Schofield D, Shrestha R. et al. Integrating exome sequencing into a diagnostic pathway for epileptic encephalopathy: evidence of clinical utility and cost effectiveness. Mol Genet Genomic Med 2018; 6 (02) 186-199