ACTL6B基因突变相关发育性癫痫性脑病伴眼底樱桃红斑儿童1例临床及遗传学分析

Genetic and clinical analysis of a novel ACTL6B gene variation related developmental epileptic encephalopathy with cherry erythema in the fundus

目的探讨ACTL6B基因变异患者临床及遗传学特征,报道新的ACTL6B基因突变,认识该基因及其表型谱。方法分析2021年3月12日就诊于首都儿科研究所附属儿童医院神经内科、经基因检测发现携带ACTL6B基因变异的发育性癫痫性脑病患儿的临床表型和基因型,并总结文献报道的携带ACTL6B基因变异患者临床表型和基因型。结果患儿为2月余龄男婴,表现为抽搐发作、发育迟滞、肌张力障碍及眼底樱桃红斑。患儿及其父母全外显子组测序示患儿携带ACTL6B基因复合杂合变异c.937-2A>G(p.?)、c.11delG(p.G4Afs*86),分别来自其父母。目前文献已报道ACTL6B基因变异(包括本患者)共42例,其中11例为新发杂合变异,31例为遗传自父母的双等位基因变异(24例纯合,7例复合杂合)。携带ACTL6B基因变异者多有癫痫、发育迟滞、运动、语言障碍及肌张力障碍,也可有特殊面容及自闭症样行为障碍。结论总结了ACTL6B基因变异患者临床及遗传学特征,首次报道了该基因变异合并眼底樱桃红斑,并报道2个新的变异。

Objective To investigate the clinical and genetic features of patients with ACTL6B gene variations,and to report novel pathogenic variations of the ACTL6B gene,summarize the clinical phenotypes and genotypes of the gene.Methods The clinical phenotypes and genotypes of a infant with developmental epileptic encephalopathy carrying the ACTL6B gene variations,who visited the Department of Neurology,Capital Institute of Pediatrics-Peking University Teaching Hospital on March 12,2021 were analyzed.The phenotypes and genotypes of patients carrying the ACTL6B gene variations reported in the literature were also summarized and analyzed.Results The proband was a 2-month-old male presented with convulsive seizures,development delay,dystonia,and cherry erythema in the fundus.The whole exome sequencing of his family showed that he carried compound heterozygous variation c.937-2A>G(p.?),c.11delG(p.G4Afs*86)which derived from his parents respectively.These 2 genotypes had not been reported.A total of 42 cases with ACTL6B gene variation were reported in the literature and in this study.There were 11 de novo heterozygous variations and 31 bi-allelic variations inherited from the parents(24 homozygous and 7 compound heterozygous).Individuals with variations tended to have epilepsy,development delay,ambulation disability,speech disability and dystonia.Minor facial dysmorphisms and autism spectrum disorder also can be seen.Conclusion This paper summarizes the clinical and genetic features of patients with ACTL6B gene variations,reports 2 novel variations and a novel combination of this gene with cherry erythema in the fundus.