【摘要】 目的总结分析CLN6纯合突变致神经元蜡样脂褐质沉积病（NCLs）患儿临床特征和基因突变类型,为NCLs患者基因诊断提供参考。方法收集2017-08-01中国医科大学附属第一医院儿科收治的1例以"语言障碍1年半,运动障碍半年,反复抽搐1周"为主诉入院,最终诊断为NCLs（晚婴型）（LINCLs）的患儿资料,总结临床资料,结合基因检测结果,并对国内报道的NCLs相关病例进行文献复习。结果患儿脑电图显示双侧大脑有多发慢波和棘慢波发放。颅脑磁共振平扫:双侧脑室后角旁条片状长T2信号影,侧脑室后角狭长,三脑室增宽,小脑脑沟裂增宽。初步诊断为脑白质病、症状性癫痫。基因检测到受检者存在CLN6纯合突变（基因参考序列NM₀17882.2）:位于第7外显子c.892G>A（p.Glu298Lys）,受检者CLN6基因所发现的纯合变异分别来自受检者父母,父母均为该位点杂合子,符合常染色体隐性遗传方式。结合临床特征及基因检测结果诊断为LINCLs。在中国知网、万方、维普数据库,通过查阅国内至今报道的所有NCLs相关文献（28篇）,共报道3例CLN6基因突变,其中2例发生杂合突变引起LINCLs,1例纯合突变引起JNCLs。本例CLN6纯合突变引起的LINCLs为我国首例报道。结论该报道为中国首例CLN6纯合突变致LINCLs,扩大了NCLs基因型数据;国内报道的NCLs患者突变基因主要是CLN1、CLN2、CLN3、CLN5、CLN6、CLN7,临床表现多表现为难治性癫痫、视力下降、智力下降、精神及运动功能障碍、性格行为改变、记忆力下降。针对不明原因的癫痫发作、脑白质病,及时行基因检测可协助早期明确诊断。更多还原

【Abstract】 Objective To collect the clinical features and gene mutation types of children with neuronal ceroid lipofuscinosis（NCLs）in China,and to help to make genetic diagnosis of NCLs patients. Methods The clinical manifestations and examinations of one case with complaints of language disorder for 1.5 years,dyskinesia for 0.5 years and repeated convulsions for one week were collected,and literatures of NCLs from China were reviewed. Results The electroencephalogram（EEG）showed multiple spikes and slow-wave discharges bilaterally. The brain MRI scan showed high hyperintensities adjacent to the bilateral posterior horns of the lateral ventricles on T2-weighted images and broadened cerebellar fissures. The "leukoencephalopathies and symptomatic epilepsy" was diagnosed. The genetic analysis showed that the proband had a homozygous missense point mutation c.892 G>A（p.Glu298 Lys）（reference sequence:NM₀17882.2）in exon 7 of CLN6 and that both his parents were heterozygous for the mutation. The diagnosis of late infantile neuronal ceroid lipofuscinosis（LINCLs）was confirmed according to the clinical features and genetic analysis results. In CNKI,WANFANG and WIPP Databases,we reviewed the relevant domestic reports about NCLs（28 articles）. A total of 3 cases of CLN6 gene mutation were reported,including 2 cases of LINCLs caused by heterozygous mutation and 1 case of JNCLs caused by homozygous mutation. Here we reported the first case of LINCLs caused by a CLN6 homozygous mutation in China. Conclusion This is the first case of LINCLs caused by CLN6 homozygous mutation reported in China. Our report expands the genotype data for NCLs.The mutant genes reported in NCLs patients are CLN1,CLN2,CLN3,CLN5,CLN6 and CLN7,and the clinical manifestations are intractable epilepsy,decreased vision,decreased intelligence,mental and motor dysfunction,personality and behavior changes,and memory decline. A gene sequencing panel for investigating unexplained seizures,leukoencephalopathies and inherited metabolic disorder can help to make the diagnosis.更多还原