Genetic overlap between dystonia and other neurologic disorders: A study of 1,100 exomes
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
35872528
DOI
10.1016/j.parkreldis.2022.07.003
PII: S1353-8020(22)00220-6
Knihovny.cz E-resources
- Keywords
- Dystonia, Exome sequencing, Molecular overlap, Panel, Shared genes,
- MeSH
- Ataxia genetics MeSH
- Dystonic Disorders * diagnosis genetics MeSH
- Dystonia * diagnosis genetics MeSH
- Exome MeSH
- Phenotype MeSH
- Humans MeSH
- Mutation MeSH
- Parkinsonian Disorders * genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
INTRODUCTION: Although shared genetic factors have been previously reported between dystonia and other neurologic conditions, no sequencing study exploring such links is available. In a large dystonic cohort, we aimed at analyzing the proportions of causative variants in genes associated with disease categories other than dystonia. METHODS: Gene findings related to whole-exome sequencing-derived diagnoses in 1100 dystonia index cases were compared with expert-curated molecular testing panels for ataxia, parkinsonism, spastic paraplegia, neuropathy, epilepsy, and intellectual disability. RESULTS: Among 220 diagnosed patients, 21% had variants in ataxia-linked genes; 15% in parkinsonism-linked genes; 15% in spastic-paraplegia-linked genes; 12% in neuropathy-linked genes; 32% in epilepsy-linked genes; and 65% in intellectual-disability-linked genes. Most diagnosed presentations (80%) were related to genes listed in ≥1 studied panel; 71% of the involved loci were found in the non-dystonia panels but not in an expert-curated gene list for dystonia. CONCLUSIONS: Our study indicates a convergence in the genetics of dystonia and other neurologic phenotypes, informing diagnostic evaluation strategies and pathophysiological considerations.
Department of Neurology Medical Faculty Mannheim Heidelberg University Mannheim Germany
Department of Neurology Medical University of Innsbruck Innsbruck Austria
Department of Neurology Zvolen Hospital Slovakia
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