Genetic Etiology Influences the Low-Frequency Components of Globus Pallidus Internus Electrophysiology in Dystonia.

Background: Elevated low-frequency activity (4-12 Hz) within the globus pallidus internus (GPi) has been consistently associated with dystonia. However, the impacts of the genetic etiology of dystonia on low-frequency GPi activity remain unclear; yet it holds importance for adaptive deep brain stimulation (DBS) treatment.

Methods: We compared the properties of GPi electrophysiology acquired from 70 microelectrode recordings (MER) trajectories of DYT-GNAL, DYT-KMT2B, DYT-SGCE, DYT-THAP1, DYT-TOR1A, DYT-VPS16, and idiopathic dystonia (iDYT) patients who underwent GPi-DBS surgery across standard frequency bands.

Combined genomics and proteomics unveils elusive variants and vast aetiologic heterogeneity in dystonia.

Dystonia is a rare-disease trait for which large-scale genomic investigations are still underrepresented. Genetic heterogeneity among patients with unexplained dystonia warrants interrogation of entire genome sequences, but this has not yet been systematically evaluated. To significantly enhance our understanding of the genetic contribution to dystonia, we (re)analyzed 2,874 whole-exome sequencing (WES), 564 whole-genome sequencing (WGS), as well as 80 fibroblast-derived proteomics datasets, representing the output of high-throughput analyses in 1,990 patients and 973 unaffected relatives from 1,877 families.

Generation of an induced pluripotent stem cell line (UCLi026-A) from a patient with ADCY5-related disease carrying the heterozygous variant c.1253G > A; (p. Arg418Gln).

Adenylyl cyclase 5 (ADCY5)-related diseases are a rare group of genetic disorders that commonly present in childhood. Heterozygous mutations in ADCY5 lead to ADCY5-related dyskinesia, comprising a wide array of disabling hyperkinetic movement disorders including chorea, myoclonus and/or dystonia. We generated an induced pluripotent stem cell line from the fibroblasts of an affected patient with the common heterozygous pathogenic variant, c.

Spiking Patterns in the Globus Pallidus Highlight Convergent Neural Dynamics across Diverse Genetic Dystonia Syndromes.

Objective: Genetic dystonia is a complex movement disorder with diverse clinical manifestations resulting from pathogenic mutations in associated genes. A recent paradigm shift emphasizes the functional convergence among dystonia genes, hinting at a shared pathomechanism. However, the neural dynamics supporting this convergence remain largely unexplored.