摘要目的:探讨1例 CLCN2基因变异导致脑白质病伴共济失调(LKPAT)患儿的临床表现及基因变异特征。 方法:回顾性分析2024年6月就诊于湖南省儿童医院1例因"间发抽搐13 d"入院患儿的临床资料。收集患儿及其父母的外周血样，对患儿进行全外显子组测序，对候选变异进行Sanger测序家系验证与致病性分析。分别以" CLCN2基因""CLC-2""脑白质病伴共济失调""脑白质病"" CLCN2 gene""chloride channel-2""leukoencephalopathy with ataxia/LKPAT""leukoencephalopathy"为中、英文关键词，检索中国知网、万方数据知识服务平台及PubMed数据库，检索时间设定为建库至2024年7月31日，筛选儿童期起病的LKPAT文献并作分析与总结。本研究通过了湖南省儿童医院医学伦理委员会的审查(批准号：HCHLL-2024-351)。 结果:①患儿为7月26 d龄男婴，其父母系近亲婚配。患儿表现为癫痫发作、发育边缘状态；头颅MRI示内囊后肢、大脑脚、脑桥及小脑中脚对称性长T 2信号影；视频脑电图示异常小儿脑电图，局灶性发作1次。②全外显子组测序提示患儿 CLCN2基因存在c.2201dup(p.Glu735Ter)纯合变异；经Sanger测序验证，该变异遗传自患儿父母；根据美国医学遗传学与基因组学学会(ACMG)与美国分子病理学协会(AMP)制定的指南，该变异被评级为致病性(PVS1＋PM3_Supporting＋PM2_Supporting)。③共检索出8篇相关文献，加上本研究病例累计报道16例儿童期起病的LKPAT患者，其中男性9例，女性7例；涉及 CLCN2基因变异12个，其中无义变异2个，错义变异3个，移码变异7个，c.61dup变异2例，c.1709G>A变异5例；16例患者首发症状包括头痛、共济失调、癫痫发作、痉挛状态、发育迟缓、腰痛、听力障碍、意向性震颤；1岁以内起病患者3例，其中2例以癫痫发作为首发症状。 结论:CLCN2：c.2201dup(p.Glu735Ter)纯合变异考虑为该LKPAT患儿的致病原因，为国内首个儿童期起病的病例。基因检测有助于儿童LKPAT的诊断，丰富了 CLCN2基因变异谱。

abstractsObjective:To explore the clinical manifestations and genetic characteristics of a child with Leukoencephalopathy with ataxia (LKPAT) caused by a CLCN2 gene variant. Methods:A retrospective analysis was conducted on the clinical data of a child admitted to Hunan Children′s Hospital in June 2024 due to " intermittent convulsions for 13 days" . Peripheral blood samples were collected from the child and his parents for whole exome sequencing, followed by Sanger sequencing validation and pathogenicity analysis of candidate variants. Literature searches were performed using the keywords " CLCN2 gene" "chloride channel-2" "leukoencephalopathy with ataxia/LKPAT" "leukoencephalopathy" in both Chinese and English on CNKI, Wanfang, and PubMed databases. The search time was set from the establishment of the databases to July 31, 2024. Childhood-onset LKPAT literature was screened and analyzed. This study was approved by the Medical Ethics Committee of Hunan Children′s Hospital (Ethics No. HCHLL-2024-351). Results:① The child was a 7-month-and-26-day-old male infant born to consanguineous parents, presenting with epileptic seizures and borderline development. Cranial MRI revealed symmetrical long T 2 signal shadows in the posterior limb of the internal capsule, cerebral peduncle, pons, and middle peduncle of the cerebellum. Video electroencephalogram (EEG) showed an abnormal childhood EEG with one focal seizure. ② Whole exome sequencing revealed a homozygous c. 2201dup (p.Glu735Ter) variant in the CLCN2 gene of the child. Sanger sequencing confirmed that the variant was inherited from both parents. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), this variant was classified as pathogenic (PVS1+ PM3_Supporting+ PM2_Supporting). ③ A total of 8 relevant literature were retrieved, together with the present case, 16 childhood-onset LKPAT patients were cumulatively reported, which consisted of 9 males and 7 females. Twelve CLCN2 gene variants were involved, including 2 nonsense variants, 3 missense variants, 7 frameshifting variants, 2 c. 61dup variants, and 5 c.1709G>A variants. The initial symptoms of the 16 patients included headache, ataxia, epileptic seizures, spasticity, developmental delay, lower back pain, hearing impairment, and intention tremor. Three patients had the onset of the disease before the age of one, of which two had epileptic seizures as the initial symptom. Conclusion:The homozygous variant CLCN2: c. 2201dup (p.Glu735Ter) is considered the pathogenic cause of LKPAT in this child, marking the first childhood-onset case reported in China. Genetic testing has facilitated the diagnosis of childhood-onset LKPAT and expanded the spectrum of CLCN2 gene mutations.