Genetic overlap between dystonia and other neurologic disorders: A study of 1,100 exomes

Dzinovic, Ivana; Boesch, Sylvia; Skorvanek, Matej; Necpal, Jan; Svantnerova, Jana; Pavelekova, Petra; Havrankova, Petra; Tsoma, Eugenia; Indelicato, Elisabetta; Runkel, Eva; Held, Valentin; Weise, David; Janzarik, Wibke; Eckenweiler, Matthias; Berweck, Steffen; Mall, Volker; Haslinger, Bernhard; Jech, Robert; Winkelmann, Juliane und Zech, Michael (2022): Genetic overlap between dystonia and other neurologic disorders: A study of 1,100 exomes. In: Parkinsonism & Related Disorders, Bd. 102: S. 1-6

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1353-8020
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 458949627
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198