神经元蜡样脂褐质沉积病五例的临床表现、基因与超微病理特点  

Clinical, genetic and pathological features of neuronal ceroid lipofuscinosis in 5 Chinese patients

作　　者：任守臣[1] 高宝勤[1] 王雅洁[1] 武小娟[1] 田朝霞[1] 孙异临[2] 

机构地区：[1]首都医科大学附属北京天坛医院儿科,100050 [2]北京神经外科研究所超微病理研究室

出　　处：《中华医学杂志》2016年第43期3504-3507,共4页National Medical Journal of China

基　　金：北京市中医药科技项目（JJ2014-26）

摘　　要：目的报道5例神经元蜡样脂褐质沉积病的临床表现、基因和超微病理改变特点。方法收集首都医科大学附属北京天坛医院儿科2013至2015年期间就诊的5例临床拟诊为神经元蜡样脂褐质沉积病患者，对4例患者及其父母提取外周血DNA，检测9个相关基因，3例行皮肤活检电镜检查。结果基因检测见1例MFSD8 1153G〉C的纯合突变，1例CLN5内含子区321－1G〉A剪切位点的纯合突变，1例为CLN6 407 G〉A和307C〉 T的复合杂合突变，其中MFSD8 1153G〉C、CLN5 321－1G〉A和CLN6 407G〉A为新发现的变异，3例患者的父母均为杂合子。1例基因检测未见异常。电镜检查示例1和例3见指纹体和嗜锇颗粒，例5见线样体和嗜锇颗粒。结论由MFSD8、CLN5和CLN6变异引起的神经元蜡样脂褐质沉积病在国内为首先报告；该病的基因型与临床表现有一定相关性；组织病理检查仍是确诊该病的金标准。ObjectiveTo report the clinical, genetic and ultrastructural pathological features of neuronal ceroid lipofuscinosis （NCLs） in 5 Chinese patients.MethodsA total of 5 patients with NCLs were collected from 2013 to 2015 diagnosed by the department of pediatrics of Beijing Tian Tan Hospital. Their clinical, electrophysiological and neuroimaging data of the patients were reviewed.A total of 9 underlying genes of NCLs were tested in 4 cases and their parents.Ultrastructural pathology by skin biopsy was performed in 3 cases respectively.ResultsWe identified two novel homozygous mutations and one novel heterozygous pathogenic mutation in 3 patients. The confirmed mutations included c. 1153G 〉C （p.Gly385Arg） MFSD8 homozygous mutation, c 321-1G 〉A CLN5 intron splice site homozygous mutation and c 407G 〉A （p.Arg136His）CLN6 heterozygous mutation, which had never been reported before. While no gene mutation was detected in the rest 1 case. Among the 3 cases received electron microscope testing of skin biopsy, 2 presented with fingerprint inclusions mixed with granular osmiophilic deposits, rectilinear profiles mixed with granular osmiophilic deposits were noted in another case.ConclusionsThe patients of NCLs caused by the mutations of MFSD8, CLN5 and CLN6 genes in Chinese population were firstly reported in this study. There are some relevence between genotype, pathomorphology and clinical presentation of NCLs. The pathomorphology is still a gold standard for the diagnosis of NCLs.

关 键 词：神经元蜡样脂褐质沉积病 基因 超微病理学 

分 类 号：R725.9[医药卫生—儿科]