Analysis of a Pedigree with Dopa-responsive Dystonia Caused by Novel Mutation of TH Gene / 中山大学学报(医学科学版)

ABSTRACT

@#【Objective】 To study the mutation characteristics of Tyrosine hydroxyls（TH） gene in a pedigree with dopa-responsive dystonia（DRD）. 【Methods】 Extraction of genomic DNA from peripheral blood of a proband and his parents and two sisters using high- throughput sequencing （NGS） method were detected on 256 known pathogenicity genes associated with dystonia and dyskinesia.【Results】Mutations on tyrosine hydroxylase（TH）gene in the exon 14 and exon 9 were detected in the proband and his eldest sister in this pedigree. They had a complex heterozygosity of c.1481C > T（p.Thr494Met）and c.943G >A（p.Gly315Ser），and one heterozygous mutation was carried by parents respectively. The mutation was not detected in his second sister and 50 people with normal phenotype controls. 【Conclusion】 The mutations of TH gene c. 1481C > T（p.Thr494Met）and c. 943G > A（p.Gly315Ser）led to the gene abnormality in DRD family，and a new mutation of TH gene was found，which expanded the relationship between DRD genotype and clinical phenotype. It is vital that early accurate diagnosis and treatment of DRD is the key to improve prognosis.