Ragona Francesca, Castellotti Barbara, Salis Barbara, Magri Stefania, DiFrancesco Jacopo C, Nardocci Nardo, Franceschetti Silvana, Gellera Cinzia, Granata Tiziana
Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Seizure. 2017 Apr;47:71-73. doi: 10.1016/j.seizure.2017.03.003. Epub 2017 Mar 6.
Mutations in the TBC1D24 gene (MIM 613577) cause familial infantile myoclonic epilepsy (FIME; 605021) and early infantile epileptic encephalopathy-16 (EIEE16; 615338), both inherited with an autosomal recessive trait. The TBC1D24 gene encodes a member of the TBC family domain proteins, involved in cell signaling and oxidative stress resistance. We studied, by a Next Generation Sequencing (NGS) target re-sequencing gene approach, the DNA of a 5 year-old girl, affected by recurrent attacks of Alternating Hemiplegia (AH) and by recurrent episodes of Epilepsia Partialis Continua (EPC). The NGS study showed the presence of two different heterozygous, probably pathogenic variants in the TBC1D24 gene, inherited in trans from her parents: the c.116C>T (p.Ala39Val) and the c.457G>A (p.Glu153Lys). This study describes for the first time the association between TBC1D24 variants and AH expanding the phenotypic spectrum of TBC1D24-related diseases and suggesting that TBC1D24 molecular analysis should be considered in the diagnostic work up of AH patients. An additional peculiar feature is the association of AH and EPC.
TBC1D24基因（MIM 613577）突变可导致家族性婴儿肌阵挛性癫痫（FIME；605021）和早期婴儿癫痫性脑病-16（EIEE16；615338），二者均为常染色体隐性遗传。TBC1D24基因编码TBC家族结构域蛋白成员，参与细胞信号传导和抗氧化应激。我们采用新一代测序（NGS）目标重测序基因方法，对一名5岁女童的DNA进行了研究，该女童患有交替性偏瘫（AH）反复发作和持续性部分性癫痫（EPC）反复发作。NGS研究显示，TBC1D24基因存在两种不同的杂合、可能致病的变异，由其父母反式遗传：c.116C>T（p.Ala39Val）和c.457G>A（p.Glu153Lys）。本研究首次描述了TBC1D24变异与AH之间的关联，扩展了TBC1D24相关疾病的表型谱，并提示在AH患者的诊断检查中应考虑TBC1D24分子分析。另一个独特特征是AH与EPC的关联。
