Abstract:

Objective　To investigate diagnosis of children’s neuronal ceroid lipofuscinosis（NCL），especially the significance of gene diagnosis. Methods　The clinical data of 5 cases of suspected NCL in our hospital from January 2013 to January 2017 were retrospectively analyzed. There were 3 boys and 2 girls，2 of whom were sister and brother. The age of onset ranged from 3 years and 4 months to 8 years and 1 month， averaged 5 years and 9 months. The first visit to our hospital ranged from 3 years and 6 months to 14 years， with an average of 8 years and 1 month. DNA of peripheral blood was extracted from 4 children with abnormal imaging and their parents and brothers，and the related genes were detected. Results　Four cases of children were diagnosed with NCL，and 1 case was diagnosed with hysteria；gene detection showed：case 1： TPP1 gene c.887-17A＞G was a shearing variant，and c.646G＞A was a missense mutation；case 2： TPP1 gene c.1015_1016 del was frameshift mutation，and c.640C＞T was nonsense mutation；the nucleotide of case 3： CLN6 gene changed to c.158T＞C（p.L53P） and c.889C＞T（p.P297S）. The parents of the 3 cases only carried one of the heterozygous variants，and the brother of case 3 had no mutation. Heterozygous mutation existed in case 4： CLN3 gene，c.1160_1169 delCAGCCTACGTinsGC，which was not detected in the mother，and there was the deletion of the paternal sample；there was loss of heterozygosity in the exon E3-E8 of the CLN3 gene，which was the true missing from mother. Five cases were followed up for 15-60 months and there was no death. Conclusion　Suspected NCL patients should be checked head MRI，electroencephalogram and gene. The gene mutation leads to NCL，such as TPP1（c.887-17A＞G，c.1015_1016 del），CLN3（c.1160_1169 delCAGCCTACGTinsGC），CLN6［（c.158T＞C（p.L53P） and c.889C＞T（p.P297S）］，are reported for the first time. Genotype is very important for NCL classification and prognosis.

Key words: neuronal ceroid lipofuscinosis, MRI, EEG, gene mutation

摘要：

目的    探讨儿童神经元蜡样脂褐质沉积症（NCL）的诊断方式，特别是基因诊断的意义。方法　回顾性分析2013年1月至2017年1月在首都医科大学宣武医院就诊的5例临床疑诊NCL的患儿资料，其中男3例、女2例，有2例为兄妹关系。患儿发病年龄3岁4个月至8岁11个月，来院首诊年龄3岁6个月至14岁。对脑影像表现异常的4例患儿及其父母、兄弟提取外周血DNA，检测相关基因。结果　4例确诊为NCL，1例为儿童癔症。基因检测：例1 TPP1基因 c.887-17A＞G为剪切变异； c.646G＞A为错义变异。例2 TPP1基因 c.1015_1016 del为移码变异； c.640C＞T为无义变异。例3 CLN6基因核苷酸改变为c.158T＞C（p.L53P）及c.889C＞T（p.P297S）。3例父母均只携带其中1个杂合变异，例3受检者哥哥未携带突变。例4 CLN3基因 c.1160_1169 delCAGCCTACGTinsGC杂合突变，母亲未检测到该突变，缺失父亲样本；CLN3基因外显子E3-E8杂合缺失，为真实缺失，母源。随访15～60个月，无死亡病例。 结论　对于怀疑NCL的患儿应及时检查头颅磁共振成像、脑电图及基因检测，导致NCL 的基因突变TPP1（c.887-17A＞G，c.1015_1016 del），CLN3（c.1160_1169 delCAGCCTACGTinsGC），CLN6［（c.158T＞C（p.L53P），c.889C＞T（p.P297S）］位点均为首次报告，基因型对于NCL的分型、判断预后十分重要。

关键词: 神经元蜡样脂褐质沉积病, 磁共振成像, 脑电图, 基因突变