PDF(Pubmed)
Abstract：
Biallelic mutations in the BRAT1 gene have been reported in cases with Lethal neonatal rigidity and multifocal seizure syndrome (RMFSL), since 2012. Clinical features include progressive encephalopathy, dysmorphic features, microcephaly, hypertonia, developmental delay, refractory epilepsy, episodic apnea, and bradycardia. More recently, biallelic BRAT1 mutations have been associated with a milder phenotype in patients with migrating focal seizures in the absence of rigidity or with nonprogressive congenital ataxia with or without epilepsy (NEDCAS). It has been proposed that the loss of function caused by BRAT1 mutations may decrease cell proliferation and migration and cause neuronal atrophy through impairment of mitochondrial homeostasis. We here report a female infant with a phenotype, electroencephalogram (EEG), and brain magnetic resonance imaging (MRI) consistent with RMFSL, whose diagnosis was indirectly formulated three years after death upon the identification in both parents of a known pathogenetic variant in the BRAT1 gene. Our report emphasizes the remarkable potential of novel genetic technologies for the diagnosis of past unsolved clinical cases.
摘要：
在致命新生儿僵直和多灶性癫痫发作综合征（RMFSL）的病例中，已经报道了BRAT1基因的双等位基因突变，自2012年。临床特征包括进行性脑病,变形特征，小头畸形,高张力症,发育迟缓,难治性癫痫,发作性呼吸暂停,和心动过缓.最近,双等位基因BRAT1突变与无强直的转移性局灶性癫痫发作患者或伴有或不伴有癫痫(NEDCAS)的非进行性先天性共济失调患者的轻度表型相关.已经提出，由BRAT1突变引起的功能丧失可能会降低细胞增殖和迁移，并通过线粒体稳态的损害引起神经元萎缩。我们在这里报道了一个具有表型的女婴，脑电图（EEG），和脑磁共振成像（MRI）与RMFSL一致，在父母双方中鉴定出BRAT1基因的已知致病变体后，其诊断是在死亡三年后间接制定的。我们的报告强调了新型遗传技术在诊断过去未解决的临床病例方面的巨大潜力。
