ArticleHuman mutation2014
Functional studies of tyrosine hydroxylase missense variants reveal distinct patterns of molecular defects in Dopa-responsive dystonia.
Article in Human mutation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Consensus Guideline for the Diagnosis and Treatment of Tyrosine Hydroxylase (TH) Deficiency.Journal of inherited metabolic disease · 2025Guideline
- Article
- Clinical and genetic spectrum of L-dopa responsive dystonia: insights from seven Egyptian cases.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Phenylalanine-tyrosine-catecholamine axis disorders: pathways, molecular diagnosis, therapeutics, and emerging translational monitoring technologies.Frontiers in molecular biosciences · 2026Review
- Early Levodopa Therapy in Tyrosine Hydroxylase Deficiency.Movement disorders clinical practice · 2025Article
- Respiratory long COVID in aged hamsters features impaired lung function post-exercise with bronchiolization and fibrosis.Nature communications · 2025Article
- Dopamine synthesis and transport: current and novel therapeutics for parkinsonisms.Biochemical Society transactions · 2024Review
- Catecholamines and Parkinson's disease: tyrosine hydroxylase (TH) over tetrahydrobiopterin (BH4) and GTP cyclohydrolase I (GCH1) to cytokines, neuromelanin, and gene therapy: a historical overview.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Segawa Syndrome, a Dramatic Response to Dopamine.Case reports in neurological medicine · 2024Article
- The genetic spectrum of a cohort of patients clinically diagnosed as Parkinson's disease in mainland China.NPJ Parkinson's disease · 2023Article
- iPSC-based modeling of THD recapitulates disease phenotypes and reveals neuronal malformation.EMBO molecular medicine · 2023Article
- Intermittent neurologic decompensation: An underrecognized presentation of tyrosine hydroxylase deficiency.JIMD reports · 2022Article
- Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation.Nature communications · 2022Article
- Segawa syndrome caused byFrontiers in genetics · 2022Article
- DOPA Homeostasis by Dopamine: A Control-Theoretic View.International journal of molecular sciences · 2021Article
- Personalized Medicine to Improve Treatment of Dopa-Responsive Dystonia-A Focus on Tyrosine Hydroxylase Deficiency.Journal of personalized medicine · 2021Review
- A six-metabolite panel as potential blood-based biomarkers for Parkinson's disease.NPJ Parkinson's disease · 2021Article
- Differential expression of striatal proteins in a mouse model of DOPA-responsive dystonia reveals shared mechanisms among dystonic disorders.Molecular genetics and metabolism · 2021Article
- Identification ofFrontiers in neurology · 2021Article
- Naturally-Occurring Rare Mutations Cause Mild to Catastrophic Effects in the Multifunctional and Cancer-Associated NQO1 Protein.Journal of personalized medicine · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Congenital tyrosine hydroxylase deficiency (THD) is found in autosomal-recessive Dopa-responsive dystonia and related neurological syndromes. The clinical manifestations of THD are variable, ranging from early-onset lethal disease to mild Parkinson disease-like symptoms appearing in adolescence. Until 2014, approximately 70 THD patients with a total of 40 different disease-related missense mutations, five nonsense mutations, and three mutations in the promoter region of the tyrosine hydroxylase (TH) gene have been reported. We collected clinical and biochemical data in the literature for all variants, and also generated mutant forms of TH variants previously not studied (N = 23). We compared the in vitro solubility, thermal stability, and kinetic properties of the TH variants to determine the cause(s) of their impaired enzyme activity, and found great heterogeneity in all these properties among the mutated forms. Some TH variants had specific kinetic anomalies and phenylalanine hydroxylase, and Dopa oxidase activities were measured for variants that showed signs of altered substrate binding. p.Arg233His, p.Gly247Ser, and p.Phe375Leu had shifted substrate specificity from tyrosine to phenylalanine and Dopa, whereas p.Cys359Phe had an impaired activity toward these substrates. The new data about pathogenic mechanisms presented are expected to contribute to develop individualized therapy for THD patients.
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