Back to Search
Start Over
Dopa-Responsive Dystonia in Han Chinese Patients: One Novel Heterozygous Mutation in GTP Cyclohydrolase 1 (GCH1) and Three Known Mutations in TH
- Source :
- Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
- Publication Year :
- 2018
- Publisher :
- International Scientific Information, Inc., 2018.
-
Abstract
- BACKGROUND This study aimed to clarify the diagnosis and expand the understanding of dopa-responsive dystonia (DRD). MATERIAL AND METHODS Relevant data from clinical diagnoses and genetic mutational analyses in 3 Han Chinese patients with sporadic DRD were collected and analyzed. Protein structure/function was predicted. RESULTS One novel mutation of c.679A>G (p.T227A) in GCH1 and 3 known mutations of c.457C>T (p.R153X), c.739G>A (p.G247S), and c.698G>A (p.R227H) in tyrosine hydroxylase (TH) have been found and predicted to be damaging or deleterious. All of the mutations were localized in conserved sequences. The iterative threading assembly refinement (I-TASSER) server generated three-dimensional (3D) atomic models based on protein sequences from the novel nonsense mutation of c.679A>G (p.T227A) in GCH1, which showed that residue 227 was located in the GCH1 active site. CONCLUSIONS Patients carrying different non-synonymous variants had remarkable variation in clinical phenotype. This study expands the spectrum of genotypes and phenotypes of DRD in the Han Chinese ethnicity, provides new insights into the molecular mechanism of DRD, and helps the diagnosis and treatment of DRD.
- Subjects :
- Male
0301 basic medicine
Heterozygote
Tyrosine 3-Monooxygenase
Nonsense mutation
Biology
Conserved sequence
03 medical and health sciences
0302 clinical medicine
Genotype-phenotype distinction
Asian People
Clinical Research
Ethnicity
medicine
Humans
Child
GTP Cyclohydrolase
Dystonia
Genetics
Tyrosine hydroxylase
Infant
Heterozygote advantage
General Medicine
medicine.disease
Pedigree
030104 developmental biology
Dystonic Disorders
Mutation
Dopamine Agonists
Metabolome
Female
Threading (protein sequence)
030217 neurology & neurosurgery
Dystonic disorder
Subjects
Details
- ISSN :
- 16433750
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Medical Science Monitor
- Accession number :
- edsair.doi.dedup.....6ed7c479e7e4831b78045d130af1ba8d