一家三同胞神经元蜡样质脂褐质沉积症7型及其MFSD8基因新突变  

Three siblings with neuronal ceroid lipofuscinosis type 7 and 2 novel mutations in their MFSD8 gene

作　　者：董慧[1] 李东晓[1] 刘怡[1] 莫若 金颖[1] 宋金青[1] 张尧[1] 杨艳玲[1] Dong Hui;Li Dongxiao;Liu Yi;Mo Ruo;Jin Ying;Song Jinqing;Zhang Yao;Yang Yanling(Department of Pediatrics,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院儿科,100034

出　　处：《中华实用儿科临床杂志》2018年第20期1550-1553,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家科技支撑计划课题（2015BAl09803）;儿科遗传性疾病分子诊断与研究北京市重点实验室（BZ0317）;北京大学第一医院科研基金资助课题（2017QN01）

摘　　要：目的神经元蜡样质脂褐质沉积症（neuronal ceroid lipofuscinosis，CLN）为一类严重的溶酶体贮积症，神经变性病，本研究拟通过对罕见的一家CLN7型三同胞的临床经过及其基因突变分析，对本症进行探讨。方法先证者，女，5岁时因“间断抽搐伴智力运动发育倒退2．5年”于2015年12月就诊，通过临床调查、头颅磁共振成像（MRI）扫描、生化代谢及基因分析进行病因诊断。结果先证者于2岁6个月起病，出现抽搐发作，伴智力运动倒退及视力下降，进行性加重。头颅MRI扫描显示弥散性脑萎缩，血液氨基酸、酯酰肉碱谱分析及尿有机酸分析未见异常，外周血白细胞棕榈酰蛋白硫脂酶、三肽酰肽酶活性正常，MFSD8基因存在c．1351-1G〉A和c．300T〉G2个致病突变，父母各携带1个突变，均为未报道的新突变，证实为CLN7型。患儿同胞哥哥临床经过与患儿相似，7岁时死于严重脑病，病因不明。弟弟2岁后出现运动障碍，4岁起出现抽搐，其MFSD8基因存在与先证者相同的c．1351-1G〉A和c．300T〉G2个致病突变，亦为CLN7型患者。结论CLN7型属于CLN的罕见类型，本研究一家三同胞诊断过程曲折，经基因分析确诊，并发现了MFSD8基因2个新突变。对于本病目前尚无有效的药物治疗方法，预后不良，在明确基因诊断基础上，对下一个同胞进行产前诊断是预防家族中疾病再发的关键。Objective The neuronal ceroid lipofuscinosis （CLN） are a group of severe lysosomal storage diseases. The patients present with clinically and genetically heterogeneous neurodegenerative disorders. This study aims to investigate the clinical characteristics and the gene mutations of a rare Chinese family with 3 siblings affected by CLN7. Methods The proband, a 5 - year - old girl, visited us because of intermittently seizures and mental retardation for 2 years and a half in December,2015. Clinical investigation, brain magnetic resonance imaging（MRI） , biochemical and the gene analysis were performed for the etiological study. Results The proband had seizures at the age of 2 and a half years, with the progressive motor deterioration, speech disturbance, mental regression and vision loss. Her brain MRI showed diffusive cerebral atrophy. The blood aminoacids, acylcarnitine and urine organic acid profiles were normal. Ly-sosomal palmitoyl protein thioesterase and tripeptidyl peptidase activities of peripheral leukocytes were normal. A com-pound heterozygous mutation of c. 1351 - 1G 〉 A and c. 300T 〉 G was detected on her MFSD8 gene, supporting the diagnosis of CLNT. Both of the 2 mutations were novel. Each of her parents carried one of the mutations. Two brothers of the proband had similar clinical process. Her elder brother died at the age of 7 due to severe eneephalopathy of unknown etiology. The younger brother showed dyskinesia from the age of 2 years and seizures from the age of 4 years. A com-pound heterozygous mutation on MFSD8 gene,c. 1351 - 1G 〉 A and c. 300T 〉 G,was found from the younger brother, as same as the proband. Conclusions CLN7 is a rare disorder of CLN. In this study, the diagnosis of the 3 siblings with similar clinical process were much delayed. Gene analysis was key for the diagnosis. Two novel mutations were found on MFSD8 of the family. There is still no effective treatment for neurol eeroid lipofuseinosis. The prognosis is poor. Based on the mutation diagnosis, prenatal diagn

关 键 词：神经元蜡样脂褐质沉积症 神经变性病 溶酶体贮积症 MFSD8基因 

分 类 号：R725.9[医药卫生—儿科]