摘要目的:总结经二代测序确诊的神经元蜡样质脂褐质沉积症2型（CLN2）一家系的临床表型及三肽基肽酶-1（TPP1）基因突变特点。方法:收集2018年6月就诊于郑州大学附属儿童医院神经内科的CLN2一 家系的临床资料，采用二代测序方法对先证者进行全外显子测序，并对家系成员进行一代Sanger验证及致病TPP1基因突变特点分析，总结临床特征。结果:先证者为3岁9个月女童，主要临床表现为全面性强直-阵挛性癫痫发作，智力正常，语言、运动轻度发育落后，眼科检查示双眼屈光不正，视力正常，无黄斑变性。头颅磁共振成像（MRI）示额颞部蛛网膜下腔增宽、脑沟加深，小脑萎缩。TPP1基因存在复合杂合突变，来自表型正常的父母，其中c.1449-1450insG（p.I484Dfs*7）来源于父亲， 为未报道的移码杂合突变，c.1417G>A（p.G473R）来源于母亲，为已知致病的错义突变，符合CLN2复合杂合突变常隐致病特点。先证者同胞哥哥3岁起病，首发症状为肌阵挛癫痫发作，现7岁伴随进行性视力障碍及智力、运动、认知功能倒退，眼科检查发现视网膜变性，头颅MRI提示全脑性萎缩， 小脑萎缩明显。TPP1致病基因及复合杂合突变位点均与先证者一致。现2岁10个月弟弟表型正常，为c.1417G>A （p.G473R）单一杂合突变，来源于母亲， 先证者父母均无临床表型。结论:CLN2是一种罕见的溶酶体贮积症，属于神经退行性疾病之一，主要临床特征为癫痫发作，进行性智力、运动倒退，视力丧失，头颅MRI提示脑萎缩，双眼黄斑变性，TPP1基因复合杂合突变c.1449-1450insG（p.I484Dfs*7）及c.1417G>A（p.G473R）是本例患儿的遗传学病因。

abstractsObjective:To summarize the clinical phenotype and tripeptidyl peptidase-1 (TPP1) gene mutation characteristics in a family with type 2 neuronal ceroid lipofuscinosis (CLN2) confirmed by second generation sequencing. Methods:The clinical data of a family with CLN2 from the Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University in June 2018 were collected. The proband was confirmed by using the whole-exome sequencing and the Sanger test of the first generation was used in the family members, and the mutation characteristics of TPP1 gene were analyzed, and the clinical features were summarized.Results:The proband is a three-year- and nine-month-old girl, presented with generalized tonic-clonic seizures, normal mental function, mild backward development of language and movement. The ophthalmic examination showed binocular ametropia, normal visual acuity, and no macular degeneration. Cranial magnetic resonance imaging (MRI) showed widening of the subarachnoid space in the frontotemporal region, deepening of the sulci, and cerebellar atrophy. There were two heterozygous mutations in the TPP1 gene, from her parents with normal phenotypes respectively. The c. 1449-1450insG (p.I484Dfs*7) mutation comes from her father, which is an unreported heterozygous mutation of code-shifting, whereas the c.1417G>A(p.G473R) mutation comes from her mother, which is a known missense mutation, consistent with the characteristic of CLN2 complex heterozygous mutation. The proband′s elder brother, whose first symptom was myoclonic seizure at the age of three, and now he is seven years old with progressive visual impairment and regression of intellectual, motor and cognitive functions. The ophthalmic examination showed retinal degeneration, and the cranial MRI showed whole-brain atrophy with obvious cerebellar atrophy. The pathogenic gene of TPP1 and the complex heterozygous mutation site were consistent with the proband. Now the proband′s younger brother is 2-year- and 10-month-old, whose phenotype is normal, with a single heterozygous mutation of c.1417G>A (p.G473R), which comes from their mother, and the parents of the proband have no clinical phenotype. Conclusions:CLN2 is a rare lysosomal storage disorder that is characterized by seizures, progressive mental and motor deterioration, loss of vision and brain atrophy on MRI, binocular macular degeneration. TPP1 complex heterozygous mutation c. 1449-1450insG(p.I484Dfs*7) and c.1417G>A(p.G473R) is the genetic cause of this case.