| Title: |
Genetic Diversity and Expanded Phenotypes in Dystonia: Insights From Large‐Scale Exome Sequencing |
| Authors: |
Mirja Thomsen; Fabian Ott; Sebastian Loens; Gamze Kilic‐Berkmen; Ai Huey Tan; Shen‐Yang Lim; Ebba Lohmann; Kaja M. Schröder; Lea Ipsen; Lena A. Nothacker; Linn Welzel; Alexandra S. Rudnik; Frauke Hinrichs; Thorsten Odorfer; Kirsten E. Zeuner; Friederike Schumann; Andrea A. Kühn; Simone Zittel; Marius Moeller; Robert Pfister; Christoph Kamm; Anthony E. Lang; Yi Wen Tay; Ana Luísa deAlmeida Marcelino; Marie Vidailhet; Emmanuel Roze; Joel S. Perlmutter; Jeanne S. Feuerstein; Victor S. C. Fung; Florence Chang; Richard L. Barbano; Steven Bellows; Aparna A. Wagle Shukla; Alberto J. Espay; Mark S. LeDoux; Brian D. Berman; Stephen Reich; Andres Deik; Andre Franke; Michael Wittig; Sören Franzenburg; Jens Volkmann; Norbert Brüggemann; H. A. Jinnah; Tobias Bäumer; Christine Klein; Hauke Busch; Katja Lohmann |
| Source: |
Annals of Clinical and Translational Neurology, Vol 12, Iss 8, Pp 1648-1659 (2025) |
| Publisher Information: |
Wiley, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Neurosciences. Biological psychiatry. Neuropsychiatry; LCC:Neurology. Diseases of the nervous system |
| Subject Terms: |
dystonia; exome sequencing; genetic heterogeneity; pathogenic variants; Neurosciences. Biological psychiatry. Neuropsychiatry; RC321-571; Neurology. Diseases of the nervous system; RC346-429 |
| Description: |
ABSTRACT Objective Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%), the etiology in most patients remains elusive. Moreover, understanding correlations between clinical manifestations and genetic variants has become increasingly complex. Methods Exome sequencing was conducted on 1924 genetically unsolved, mainly late‐onset isolated dystonia patients, recruited primarily from two dystonia registries (DysTract and the Dystonia Coalition). Rare variants in genes previously linked to dystonia (n = 406) were examined, confirmed via Sanger sequencing, and analyzed for segregation when possible. Results We identified 137 distinct likely pathogenic/pathogenic variants (according to ACMG criteria) across 51 genes in 163/1924 patients, including 153/1895 index patients (diagnostic yield 8.1%). The strongest predictors of a genetic diagnosis were generalized dystonia (28.6% yield) and age at onset (20.4% yield in patients with onset |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2328-9503 |
| Relation: |
https://doaj.org/toc/2328-9503 |
| DOI: |
10.1002/acn3.70100 |
| Access URL: |
https://doaj.org/article/9ac7f4ecc7d7456ebe8b5a2a42e1860b |
| Accession Number: |
edsdoj.9ac7f4ecc7d7456ebe8b5a2a42e1860b |
| Database: |
Directory of Open Access Journals |