Clinical characteristics and genetic analysis of patients with autosomal recessive dopa-responsive dystonia / 中华实用儿科临床杂志

ABSTRACT

Objective@#To analyze the clinical characteristics and gene mutation of autosomal recessive dopa-responsive dystonia(AR-DRD), and to explore its therapeutic effect, follow-up findings and molecular genetic me-chanism.@*Methods@#The whole exome sequencing, which based on next-generation sequencing, was performed in 6 movement-disordered patients who denied family history at the outpatient clinic of Children′s Hospital Affiliated to Capital Institute of Pediatrics from April 2016 to September 2017.The mutations identified in probands were then confirmed in probands and their parents by Sanger sequencing in order to analyze the cause of mutations.@*Results@#(1)Clinical features: the onset of 6 patients was around infancy, complicated with muscle weakness and abnormal muscle tone.(2)Gene mutation analysis: All 6 patients carried TH gene mutations.Five patients were of complex heterozygosis mutations, 1 patient was of homozygosis mutation.Five mutations were detected: c.605 G>A, c.601 C>T, c.364C>T, c.1412_1413insCCCCCAGGCCGTGC and c. 646G>A.(3)Therapeutic effect: all 6 patients achieved improvement of motor function after dopamine treatment, and they presented the different degrees of improvement in muscle tone and muscle strength.@*Conclusions@#The AR-DRD patients who carried c. 605 G>A mutation have a good therapeutic effect treated with L-Dopamine.This mutation may be a common mutation site of mild to moderate defective AR-DRD at home and abroad.The frameshift mutation c. 1412_1413insCCCCCAGGCCGTGC is a new TH gene pathogenicity mutation site discovered by this study.