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