Long‐Read Sequencing: The Third Generation of Diagnostic Testing for Dystonia DOI Creative Commons
Thomas Wirth, Kishore R. Kumar, Michael Zech

et al.

Movement Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Abstract Long‐read sequencing methodologies provide powerful capacity to identify all types of genomic variations in a single test. platforms such as Oxford Nanopore and PacBio have the potential revolutionize molecular diagnostics by reaching unparalleled accuracies genetic discovery long‐range phasing. In field dystonia, promising results come from recent pilot studies showing improved detection disease‐causing structural variants repeat expansions. Increases throughput ongoing reductions cost will facilitate incorporation long‐read approaches into mainstream diagnostic practice. Although these developments are likely transform clinical care, there is currently discrepancy between benefits application this technique dystonia. review we highlight current opportunities limitations adopting methods for investigation patients with We examples integration evaluation study pathomechanisms individuals dystonic disorders. The goal article stimulate research optimization analysis strategies thus enabling more precise understanding underlying etiology future. © 2025 Author(s). Movement Disorders published Wiley Periodicals LLC on behalf International Parkinson Disorder Society.

Language: Английский

Purine Metabolism and Dystonia: Perspectives of a Long‐Promised Relationship DOI Creative Commons
Ugo Sorrentino, Audrey G. O’Neill, Justin M. Kollman

et al.

Annals of Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Dystonia research focuses on the identification of converging biological pathways, allowing to define molecular drivers that serve as treatment targets. We summarize evidence supporting concept aberrations in purine metabolism intersect with dystonia pathogenesis. The recent discovery IMPDH2 ‐related introduced a gain‐of‐function paradigm purinergic system defects, offering new perspectives understand purine‐pool imbalances brain diseases. discuss commonalities between known dystonia‐linked mechanisms and emerging from studies disorders including Lesch–Nyhan disease. Together, we hypothesize greater appreciation relevance perturbances can offer fresh avenues for therapeutic intervention. ANN NEUROL 2025

Language: Английский

Citations

0
AOPEP-related autosomal recessive dystonia: update on Zech-Boesch syndrome DOI
Sylvia Boesch, Michael Zech

Journal of Medical Genetics, Journal Year: 2025, Volume and Issue: unknown, P. jmg - 110656

Published: March 27, 2025

Gene discovery efforts have contributed to a better understanding of the molecular causes dystonia, but knowledge individual monogenic forms remains limited. This review seeks summarise all available data on recently identified autosomal recessive subtype dystonia caused by variants in AOPEP , focusing geographical origins affected families, mutational spectrum, phenotypic expressions and pathophysiology. -related documented as Zech-Boesch syndrome Online Mendelian Inheritance Man database, has been diagnosed cohorts around globe including under-represented populations with increased rates consanguinity. Predictably leading loss protein function, majority (74%) disease-associated alleles are protein-truncating comprising homozygous compound heterozygous stop-gain, frameshift splice-site changes. The dystonic disorder shows onset from childhood fourth decade generalises significant proportion cases (60%). Variable expressivity age-related penetrance likely play role manifestation condition, consistent occasional occurrence pathogenic subjects without diagnosis dystonia. encodes aminopeptidase O, proteolytic processing enzyme that is preferentially expressed glia potentially linked endosomal-lysosomal pathways. worldwide relevance for genetic Future research ˋs cellular metabolism may provide new insights into pathogenesis yet-unidentified therapeutic targets.

Language: Английский

Citations

0
Reduced Penetrance in Interferonopathy‐Associated Dystonia: Hope for Clues to Mechanism? DOI
Martin Krenn, Michael Zech

Movement Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Language: Английский

Citations

0
New Progressive Generalized Dystonia Phenotype in a Patient with NBEA‐Related Neurodevelopmental Disease DOI
Michał Schinwelski, Magdalena Krygier, Emilia J. Sitek

et al.

Movement Disorders Clinical Practice, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Language: Английский

Citations

0
Long‐Read Sequencing: The Third Generation of Diagnostic Testing for Dystonia DOI Creative Commons
Thomas Wirth, Kishore R. Kumar, Michael Zech

et al.

Movement Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Abstract Long‐read sequencing methodologies provide powerful capacity to identify all types of genomic variations in a single test. platforms such as Oxford Nanopore and PacBio have the potential revolutionize molecular diagnostics by reaching unparalleled accuracies genetic discovery long‐range phasing. In field dystonia, promising results come from recent pilot studies showing improved detection disease‐causing structural variants repeat expansions. Increases throughput ongoing reductions cost will facilitate incorporation long‐read approaches into mainstream diagnostic practice. Although these developments are likely transform clinical care, there is currently discrepancy between benefits application this technique dystonia. review we highlight current opportunities limitations adopting methods for investigation patients with We examples integration evaluation study pathomechanisms individuals dystonic disorders. The goal article stimulate research optimization analysis strategies thus enabling more precise understanding underlying etiology future. © 2025 Author(s). Movement Disorders published Wiley Periodicals LLC on behalf International Parkinson Disorder Society.

Language: Английский

Citations

0