ArticleAnnals of neurology2013
Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene.
Article in Annals of neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 142 citations in OpenAlex.
- Case Report of Bilateral Subthalamic Nucleus Deep Brain Stimulation in an Adolescent TUBB4A Patient: She Can Sit on a Horse.Movement disorders clinical practice · 2025Article
- Rediscovery of the Tubulin β-4A p.Arg2Gly Variant in Whispering Dysphonia: A Report from Austria.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Pediatric Genetic Dystonias: Current Diagnostic Approaches and Treatment Options.Life (Basel, Switzerland) · 2025Review
- Insights on the Shared Genetic Landscape of Neurodevelopmental and Movement Disorders.Current neurology and neuroscience reports · 2025Review
- The natural history of variable subtypes in pediatric-onset TUBB4A-related leukodystrophy.Molecular genetics and metabolism · 2025Article
- tubg1 Somatic Mutants Show Tubulinopathy-Associated Neurodevelopmental Phenotypes in a Zebrafish Model.Molecular neurobiology · 2025Article
- LncRNA TubAR complexes with TUBB4A and TUBA1A to promote microtubule assembly and maintain myelination.Cell discovery · 2024Article
- Molecular Pathogenic Mechanisms of Hypomyelinating Leukodystrophies (HLDs).Neurology international · 2023Review
- Gross Motor Function in Pediatric OnsetJournal of child neurology · 2023Article
- Insights on the Role of α- and β-Tubulin Isotypes in Early Brain Development.Molecular neurobiology · 2023Review
- Roles of the cytoskeleton in human diseases.Molecular biology reports · 2023Review
- Novel loss of function mutation inFrontiers in cellular neuroscience · 2023Article
- Understanding molecular mechanisms and predicting phenotypic effects of pathogenic tubulin mutations.PLoS computational biology · 2022Article
- Functional Investigation of TUBB4A Variants Associated with Different Clinical Phenotypes.Molecular neurobiology · 2022Article
- DYT-TUBB4A (DYT4 Dystonia): Clinical Anthology of 11 Cases and Systematized Review.Movement disorders clinical practice · 2022Review
- The Patho-Neurophysiological Basis and Treatment of Focal Laryngeal Dystonia: A Narrative Review and Two Case Reports Applying TMS over the Laryngeal Motor Cortex.Journal of clinical medicine · 2022Review
- H-ABC- and dystonia-causingScience advances · 2022Article
- A dominant tubulin mutation causes cerebellar neurodegeneration in a genetic model of tubulinopathy.Science advances · 2022Article
- In-silico phenotype prediction by normal mode variant analysis in TUBB4A-related disease.Scientific reports · 2022Article
- Acquisition of Developmental Milestones in Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum and Other TUBB4A-Related Leukoencephalopathy.Journal of child neurology · 2021Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 12 institutions in 6 countries.
Funding
Abstract
objectiveA study was undertaken to identify the gene underlying DYT4 dystonia, a dominantly inherited form of spasmodic dysphonia combined with other focal or generalized dystonia and a characteristic facies and body habitus, in an Australian family.
methodsGenome-wide linkage analysis was carried out in 14 family members followed by genome sequencing in 2 individuals. The index patient underwent a detailed neurological follow-up examination, including electrophysiological studies and magnetic resonance imaging scanning. Biopsies of the skin and olfactory mucosa were obtained, and expression levels of TUBB4 mRNA were determined by quantitative real-time polymerase chain reaction in 3 different cell types. All exons of TUBB4 were screened for mutations in 394 unrelated dystonia patients.
resultsThe disease-causing gene was mapped to a 23cM region on chromosome 19p13.3-p13.2 with a maximum multipoint LOD score of 5.338 at markers D9S427 and D9S1034. Genome sequencing revealed a missense variant in the TUBB4 (tubulin beta-4; Arg2Gly) gene as the likely cause of disease. Sequencing of TUBB4 in 394 unrelated dystonia patients revealed another missense variant (Ala271Thr) in a familial case of segmental dystonia with spasmodic dysphonia. mRNA expression studies demonstrated significantly reduced levels of mutant TUBB4 mRNA in different cell types from a heterozygous Arg2Gly mutation carrier compared to controls.
interpretationA mutation in TUBB4 causes DYT4 dystonia in this Australian family with so-called whispering dysphonia, and other mutations in TUBB4 may contribute to spasmodic dysphonia. Given that TUBB4 is a neuronally expressed tubulin, our results imply abnormal microtubule function as a novel mechanism in the pathophysiology of dystonia.
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