2例Lesch-Nyhan综合征患儿及家系临床表型和基因突变分析

目的探讨Lesch-Nyhan综合征(Lesch-Nyhan syndrome, LNS)的临床表型和基因突变类型。方法收集2例LNS家系中先证者的临床资料,包括病史、体格检查及生化检查,抽取先证者及其家系成员外周血,采用二代高通量测序法进行基因检测,并采用Sanger测序法进行位点验证及家系验证。结果 2例先证者围生期无明显异常,均于6个月内出现发育落后,1岁6个月后出现自残行为,血尿酸增高,2例先证者HPRT1基因均存在突变,先证者1为c.609+5G>A的剪接突变,先证者2为c.212G>A,p.G71D的错义突变。结论伴尿酸增高的发育落后患儿应警惕LNS的发生,基因检测有助于该病的早期诊断。

Clinical phenotype and gene mutation in 2 children with Lesch-Nyhan syndrome and their families

Objective To investigate the clinical phenotype and gene mutation type of Lesch-Nyhan syndrome(LNS) in 2 children and their families. Methods The clinical data of two probands from LNS families were collected, including medical history, physical examination and biochemical examination results. The peripheral blood from the probands and their family members were extracted for genetic tests by the second generation sequencing method, and site validation and pedigree validation were performed by Sanger sequencing method. Results These two probands were found no obvious abnormality in perinatal period, but developmental retardation in 6 months and self-mutilation and increased uric acid after the age of 1.5 year. The HPRT1 gene mutation was found in both of the two probands, c.609+5 G>A splicing mutation of proband 1, and c.212 G>A p.G71 D missense mutation of proband 2. Conclusion The children with developmental retardation complicated with hyperuricemia should be considered Lesch-Nyhan syndrome. Genetic test contributes to the early diagnosis of LNS.