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Sorrentino, U. ; Brugger, M.* ; Saparov, A. ; Dzinovic, I. ; Harrer, P. ; Lösecke, S.* ; Derderian, K.* ; Pavlov, M. ; Kopajtich, R. ; Prokisch, H. ; Iuso, A. ; Mazurkiewicz-Bełdzińska, M.* ; Weiss, D.* ; Ludwig, C.* ; Abele, M.* ; Mergner, J.* ; Winkelmann, J. ; Brunet, T.* ; Schinwelski, M.* ; Graf, E.* ; Kloth-Stachnau, K.* ; Herget, T.* ; Krygier, M.* ; Zech, M.

Resolving complex structural variants in undiagnosed rare movement disorders via multimodal genomics and multi-omics.

Mov. Disord., DOI: 10.1002/mds.70427 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
BACKGROUND: Long-read sequencing and multi-omic analytical frameworks are increasingly being adopted in rare disease diagnostics. However, clinical workflows comprehensively integrating these methodologies remain uncommon. OBJECTIVE: This study aimed to assess the potential and limitations of integrating long-read genomic, transcriptomic, and proteomic analyses to characterize complex structural variants. METHODS: Two unrelated patients presenting with dystonia and comorbid neurological features underwent nanopore-based long-read DNA sequencing. In patient 1, complementary transcriptomic and proteomic analyses were performed. RESULTS: The workflow enabled the identification and characterization of two pathogenic complex structural variants: a homozygous AluY-mediated inversion disrupting PANK2, underlying neurodegeneration with brain iron accumulation (patient 1), and a heterozygous de novo 16p13.3 duplication-triplication event associated with an atypical dystonia-parkinsonism phenotype (patient 2). CONCLUSIONS: Our findings underscore the diagnostic potential of integrated long-read and multi-omic approaches for complex structural variant characterization, while illustrating persistent limitations of automated pipelines and highlighting unpredictable relationships between genomic, transcriptomic, and proteomic findings. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Complex Structural Variants ; Dystonia ; Long‐read Sequencing ; Multi‐omics ; Nanopore Technology
ISSN (print) / ISBN 0885-3185
e-ISSN 1531-8257
Zeitschrift Movement Disorders
Verlag Wiley
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)