临床儿科杂志 ›› 2020, Vol. 38 ›› Issue (2): 110-.doi: 10.3969/j.issn.1000-3606.2020.02.008

• 综合报道 • 上一篇    下一篇

HPRT1 基因相关神经系统异常综合征1 例报告

赵培伟, 毕博, 谭黎, 林俊, 何学莲   

  1. 华中科技大学同济医学院附属武汉儿童医院(湖北武汉 430016)
  • 发布日期:2020-02-20
  • 通讯作者: 何学莲 电子信箱:Hexuelian2013@hotmail.com

Clinical features of HPRT-related neurological dysfunction and genetic analysis

 ZHAO Peiwei, BI Bo, TAN Li, LIN Jun, HE Xuelian   

  1. Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430016, Hubei, China
  • Published:2020-02-20

摘要: 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1 404.7 μmol/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。

关键词:  HPRT相关神经系统异常综合征; HPRT1基因; 高通量测序; 临床特点

Abstract:  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 (1404.7 μmol/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.

Key words: HPRT-related neurological dysfunction; HPRT1 gene; NGS; clinical phenotype