HPRT1基因相关神经系统异常综合征1例报告

Clinical features of HPRT-related neurological dysfunction and genetic analysis

目的探讨HPRT1基因相关的神经系统异常综合征(HRND)的临床表现及基因突变特点。方法回顾分析1例以发育迟缓、高尿酸血症为表现的HRND患儿的临床资料及基因全外显子测序和验证结果。复习文献,比较相似基因型患者的临床表型,并在RNA水平探讨基因突变对蛋白功能的影响。结果患儿,男,3岁4个月。面容未见异常,语言、运动发育均落后,四肢活动受限,双下肢可部分持重,双足外翻,四肢肌力低下,活动及情绪紧张时四肢肌张力增高,不自主动作增多。尿酸1404.7μmol/L,Y痕迹蛋白1.64 mg/L,乳酸脱氢酶539 U/L,乳酸脱氢酶同工酶84 U/L。脑电图、肌电图、头颅磁共振未见明显异常。全外显子测序结果显示,HPRT1基因存在c.319-2A>T剪接位点突变,其母亲为携带者,该突变可导致HPRT1基因编码的RNA错误加工(缺少外显子3)。结论HPRT1基因c.319-2A>T剪接突变是导致HRND的遗传病因,全外显子测序技术可协助临床确诊。

Objective To investigate the clinical features and gene mutation of a patient diagnosed with HPRT-related neurological dysfunction(HRND).Method Genetic analysis of this patient was performed using whole exome sequencing,Sanger sequencing was used to verify the results,and literatures about clinical features of HRND with similar genotype were reviewed.Effect of mutation on RNA splicing was investigated.Results The patient was a 3 years 4 months old boy with global developmental delay,presented with limited extremities,low muscle strength,partially weighed legs and valgus feet.Hypermyotonia and frequent involuntary movements were observed in the patient during activity and emotional stress.Uric acid increased significantly(1404.7μmol/L),and Y trace protein also increased(1.64 mg/L).The level of lactate dehydrogenase was 539U/L and its isozyme(LD1)84U/L(15-65 U/L).EEG,EMG and CT/MRI results were normal.We found a c.319-2A>T hemizygous mutation in HPRT1 gene inherited from his mother.This mutation affects RNA processing by producing a transcript with exon3 skipping.Conclusion The splice site mutation(c.319-2A>T)of HPRT1 is the genetic cause of HRND in this patient,and WES technology can assist clinical diagnosis.