E-resources
Peer reviewed
Open access
-
Thomsen, Mirja; Marth, Katrin; Loens, Sebastian; Everding, Judith; Junker, Johanna; Borngräber, Friederike; Ott, Fabian; Jesús, Silvia; Gelderblom, Mathias; Odorfer, Thorsten; Kuhlenbäumer, Gregor; Kim, Han‐Joon; Schaeffer, Eva; Becktepe, Jos; Kasten, Meike; Brüggemann, Norbert; Pfister, Robert; Kollewe, Katja; Krauss, Joachim K.; Lohmann, Ebba; Hinrichs, Frauke; Berg, Daniela; Jeon, Beomseok; Busch, Hauke; Altenmüller, Eckart; Mir, Pablo; Kamm, Christoph; Volkmann, Jens; Zittel, Simone; Ferbert, Andreas; Zeuner, Kirsten E.; Rolfs, Arndt; Bauer, Peter; Kühn, Andrea A.; Bäumer, Tobias; Klein, Christine; Lohmann, Katja
Movement disorders, March 2024, 2024-Mar, 2024-03-00, 20240301, Volume: 39, Issue: 3Journal Article
Background Pathogenic variants in several genes have been linked to genetic forms of isolated or combined dystonia. The phenotypic and genetic spectrum and the frequency of pathogenic variants in these genes have not yet been fully elucidated, neither in patients with dystonia nor with other, sometimes co‐occurring movement disorders such as Parkinson's disease (PD). Objectives To screen >2000 patients with dystonia or PD for rare variants in known dystonia‐causing genes. Methods We screened 1207 dystonia patients from Germany (DysTract consortium), Spain, and South Korea, and 1036 PD patients from Germany for pathogenic variants using a next‐generation sequencing gene panel. The impact on DNA methylation of KMT2B variants was evaluated by analyzing the gene's characteristic episignature. Results We identified 171 carriers (109 with dystonia 9.0%; 62 with PD 6.0%) of 131 rare variants (minor allele frequency <0.005). A total of 52 patients (48 dystonia 4.0%; four PD 0.4%, all with GCH1 variants) carried 33 different (likely) pathogenic variants, of which 17 were not previously reported. Pathogenic biallelic variants in PRKRA were not found. Episignature analysis of 48 KMT2B variants revealed that only two of these should be considered (likely) pathogenic. Conclusion This study confirms pathogenic variants in GCH1, GNAL, KMT2B, SGCE, THAP1, and TOR1A as relevant causes in dystonia and expands the mutational spectrum. Of note, likely pathogenic variants only in GCH1 were also found among PD patients. For DYT‐KMT2B, the recently described episignature served as a reliable readout to determine the functional effect of newly identified variants. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Author
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.