ArticleAnnals of neurology2014
Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia.
Article in Annals of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 123 citations in OpenAlex.
- Modulation of striatal cAMP levels: A key pathway in the treatment of hyperkinetic movement disorders.iScience · 2026Article
- Mixed Movement Disorder Caused byCase reports in neurological medicine · 2026Article
- Mice carrying the human dopamine D2 receptor pathogenic mutation p.Met374Arg exhibit hyperactivity and aberrant D2 receptor function.Molecular pharmacology · 2025Article
- Treatment Efficacy of Theophylline in ADCY5-Related Dyskinesia: A Retrospective Case Series Study.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Comparison of the function of two novel human dopamine D2 receptor variants identifies a likely mechanism for their pathogenicity.Biochemical pharmacology · 2024Article
- Structure of adenylyl cyclase 5 in complex with Gβγ offers insights into ADCY5-related dyskinesia.Nature structural & molecular biology · 2024Article
- Scoping Review on ADCY5-Related Movement Disorders.Movement disorders clinical practice · 2023Article
- A Study of Dopaminergic Pathway in Neurologic Wilson Disease with Movement Disorder.Molecular neurobiology · 2023Article
- Gait Abnormalities and Aberrant D2 Receptor Expression and Signaling in Mice Carrying the Human Pathogenic MutationMolecular pharmacology · 2023Article
- Article
- Developing CIRdb as a catalog of natural genetic variation in the Canary Islanders.Scientific reports · 2022Article
- Discovery of levodopa-induced dyskinesia-associated genes using genomic studies in patients and Drosophila behavioral analyses.Communications biology · 2022Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- Expression and functions of adenylyl cyclases in the CNS.Fluids and barriers of the CNS · 2022Review
- Structural basis of adenylyl cyclase 9 activation.Nature communications · 2022Article
- The Emerging Role of Phosphodiesterases in Movement Disorders.Movement disorders : official journal of the Movement Disorder Society · 2021Review
- GPharmacological reviews · 2021Review
- Homozygous ADCY5 mutation causes early-onset movement disorder with severe intellectual disability.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Article
- Emerging and converging molecular mechanisms in dystonia.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
- Genetic updates on paroxysmal dyskinesias.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 8 institutions in 2 countries.
Funding
Abstract
objectiveTo identify the cause of childhood onset involuntary paroxysmal choreiform and dystonic movements in 2 unrelated sporadic cases and to investigate the functional effect of missense mutations in adenylyl cyclase 5 (ADCY5) in sporadic and inherited cases of autosomal dominant familial dyskinesia with facial myokymia (FDFM).
methodsWhole exome sequencing was performed on 2 parent-child trios. The effect of mutations in ADCY5 was studied by measurement of cyclic adenosine monophosphate (cAMP) accumulation under stimulatory and inhibitory conditions.
resultsThe same de novo mutation (c.1252C>T, p.R418W) in ADCY5 was found in both studied cases. An inherited missense mutation (c.2176G>A, p.A726T) in ADCY5 was previously reported in a family with FDFM. The significant phenotypic overlap with FDFM was recognized in both cases only after discovery of the molecular link. The inherited mutation in the FDFM family and the recurrent de novo mutation affect residues in different protein domains, the first cytoplasmic domain and the first membrane-spanning domain, respectively. Functional studies revealed a statistically significant increase in β-receptor agonist-stimulated intracellular cAMP consistent with an increase in adenylyl cyclase activity for both mutants relative to wild-type protein, indicative of a gain-of-function effect.
interpretationFDFM is likely caused by gain-of-function mutations in different domains of ADCY5-the first definitive link between adenylyl cyclase mutation and human disease. We have illustrated the power of hypothesis-free exome sequencing in establishing diagnoses in rare disorders with complex and variable phenotype. Mutations in ADCY5 should be considered in patients with undiagnosed complex movement disorders even in the absence of a family history.
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