Abstract: Objective　This study aims to summarize the clinical manifestations and genetic information of Chinese patients with infancy-onset Lesch-Nyhan Syndrome（LNS）. Methods　Whole-exome sequencing（WES） was conducted on 4 patients referred to the Department of Neurology，Children’s Hospital of Capital Institute of Pediatrics from 2017 to 2018，who were characterized by hyperuricemia，psychomotor delay，dystonia with or without self-mutilation. The Sanger sequencing was used for verification. The clinical and genetic information of LNS patients reported as Chinese origin were collected fromPubmed，Zhiwang and Wanfang public databases. Results　Four patients admitted in our hospital were diagnosed with LNS. Four pathogenic mutations in HPRT1 gene were identified from 4 patients，confirming their genetic diagnoses with LNS：two missense（c.49T＞A，p.Y17N and c.133A＞G，p.R45G），a nonsense（c.325C＞T，p.Q109*） and a frameshift（c.419delG，p.G140Afs*26） mutation.Two mutations（p.Y17N and p.G140Afs*26） among them are novel. After retrieving another 11 Chinese patients with infancy-onset LNS，the phenotype-genotype analysis showed three core phenotypes including intellectual delay，hyperuricemia，psychomotor delay were identified with complete penetrance，and patients with disrupt HPRT1 mutations present self-mutilation more early that ones with missense mutation. Conclusion　This study reported the clinical manifestations and genetic information of Chinese patients with infancy-onset LNS，and it broaden the mutation spectrum of HPRT1 in LNS patients. The potential correlations between phenotypes and genotypes were discussed as well. Genetic screening of LNS is highly recommended for the neonates with hyperuricemia and neurological disorders，which are helpful for early diagnosis and treatment.

Key words: Lesch-Nyhan syndrome, whole-exome sequencing, HPRT1 gene, hyperuricemia, self-mutilation

摘要： 目的　分析婴儿期发病Lesch-Nyhan综合征（LNS）患者临床特点以及相关基因突变情况。方法　对2017—2018年就诊于首都儿科研究所附属儿童医院的4例尿酸升高、运动发育迟缓、肌张力障碍伴或不伴有自残行为的婴儿患者进行全外显子基因检测，生物信息学分析筛选致病性变异，并对核心家系成员采用Sanger测序分析突变来源。总结整理Pubmed、知网和万方数据库报道过的婴儿期发病LNS中国患者的临床特点及基因突变情况。结果　4例均携带HPRT1基因致病性突变，符合LNS遗传诊断。突变分别为2个错义突变（c.49T＞A，p.Y17N和c.133A＞G，p.R45G），1个无义突变（c.325C＞T，p.Q109*）和1个移码突变（c.419delG，p.G140Afs*26），其中p.Y17N和p.G140Afs*26为未报道的新突变。回顾文献收集 11例婴儿期发病的中国LNS患者，HPRT1基因型与临床表型的相关性分析发现了智力迟缓、运动发育迟缓、高尿酸血症为核心表型，且出现比例为100%；和错义突变相比，截短性突变较早出现自我伤害表型。结论　该研究描述了婴儿期发病的中国LNS患者临床与基因信息，补充了HPRT1基因突变谱，对临床表现为高尿酸血症合并神经系统异常的儿童患者进行LNS基因筛查将有助于早期LNS诊断和治疗。

关键词: Lesch-Nyhan综合征, 全外显子基因检测, HPRT1基因, 高尿酸血症, 自毁容貌