ArticleAmerican journal of human genetics2015
Recessive mutations in the α3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.
Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 84 citations in OpenAlex.
- Comparative Genomic Screening Identifies Developmental Constraint Loci Underscoring the Phenotypic Evolution of Syngnathids.Integrative zoology · 2026Article
- Early-Onset Isolated Dystonia Associated with COL6A3 Mutation Responsive to Deep Brain Stimulation.Movement disorders clinical practice · 2024Article
- Plasma acellular transcriptome contains Parkinson's disease signatures that can inform clinical diagnosis.medRxiv : the preprint server for health sciences · 2024Article
- Whole-exome sequencing in a cohort of Chinese patients with isolated cervical dystonia.Heliyon · 2024Article
- Exome and genome sequencing to unravel the precise breakpoints of partial trisomy 6q and partial Monosomy 2q.BMC pediatrics · 2023Article
- Integration of genetic fine-mapping and multi-omics data reveals candidate effector genes for hypertension.American journal of human genetics · 2023Article
- Dystonias: Clinical Recognition and the Role of Additional Diagnostic Testing.Seminars in neurology · 2023Article
- Genetic analysis of dystonia-related genes in Parkinson's disease.Frontiers in aging neuroscience · 2023Article
- A novel compound heterozygous mutation ofFrontiers in neurology · 2023Article
- Article
- Collagen VI deficiency causes behavioral abnormalities and cortical dopaminergic dysfunction.Disease models & mechanisms · 2022Article
- 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
- Single-Nucleus RNA Sequencing Reveals that Decorin Expression in the Amygdala Regulates Perineuronal Nets Expression and Fear Conditioning Response after Traumatic Brain Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Collagen VI Regulates Motor Circuit Plasticity and Motor Performance by Cannabinoid Modulation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- A study of elective genome sequencing and pharmacogenetic testing in an unselected population.Molecular genetics & genomic medicine · 2021Article
- Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson's disease.BMC neurology · 2021Article
- Isolated dystonia: clinical and genetic updates.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
- Genetic Dystonias: Update on Classification and New Genetic Discoveries.Current neurology and neuroscience reports · 2021Review
- What can we learn from common variants associated with unexpected phenotypes in rare genetic diseases?Orphanet journal of rare diseases · 2021Article
- Collagen proteins are found also within the neural parenchyma in the healthy CNS.AIMS neuroscience · 2021Article
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15 authors at 5 institutions in 3 countries.
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Abstract
Isolated dystonia is a disorder characterized by involuntary twisting postures arising from sustained muscle contractions. Although autosomal-dominant mutations in TOR1A, THAP1, and GNAL have been found in some cases, the molecular mechanisms underlying isolated dystonia are largely unknown. In addition, although emphasis has been placed on dominant isolated dystonia, the disorder is also transmitted as a recessive trait, for which no mutations have been defined. Using whole-exome sequencing in a recessive isolated dystonia-affected kindred, we identified disease-segregating compound heterozygous mutations in COL6A3, a collagen VI gene associated previously with muscular dystrophy. Genetic screening of a further 367 isolated dystonia subjects revealed two additional recessive pedigrees harboring compound heterozygous mutations in COL6A3. Strikingly, all affected individuals had at least one pathogenic allele in exon 41, including an exon-skipping mutation that induced an in-frame deletion. We tested the hypothesis that disruption of this exon is pathognomonic for isolated dystonia by inducing a series of in-frame deletions in zebrafish embryos. Consistent with our human genetics data, suppression of the exon 41 ortholog caused deficits in axonal outgrowth, whereas suppression of other exons phenocopied collagen deposition mutants. All recessive mutation carriers demonstrated early-onset segmental isolated dystonia without muscular disease. Finally, we show that Col6a3 is expressed in neurons, with relevant mRNA levels detectable throughout the adult mouse brain. Taken together, our data indicate that loss-of-function mutations affecting a specific region of COL6A3 cause recessive isolated dystonia with underlying neurodevelopmental deficits and highlight the brain extracellular matrix as a contributor to dystonia pathogenesis.
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