Unified long-read panel for Parkinson’s and repeat expansion disorders
Abstract In this study, we designed a gene panel based on Nanopore long-read sequencing using adaptive sampling, targeting n = 564 genes associated with Parkinson’s disease (PD) and repeat expansion disorders. We investigated its diagnostic utility in n = 18 patients with (1) pathogenic variants in LRRK2 , PRKN , SNCA , and RAB32 ( n = 7); (2) idiopathic PD or FTD negative for known genetic causes ( n = 3); (3) repeat expansions in ATXN1 , ATXN2 , ATXN3 , C9orf72 , DAB1 , FGF14 , HTT , and TAF1 -SVA ( n = 8). Three individuals were multiplexed per flow cell, achieving a mean coverage of 24X (SD = ± 9X) per sample. Ultimately, 17/20 (85%; Clopper–Pearson 95% CI: 62–97%) expected pathogenic variants were identified; i.e., an SNCA triplication and two repeat expansions in C9orf72 and TAF1 -SVA were missed. Additional variants in STXBP2 , AP4S1 , RARS2 , ALS2 , and CNBP were identified in five patients. Adaptive sampling is a versatile genetic diagnostic tool in neurodegenerative disorders, while enabling cost-effective multiplexing. Further validation and improvements in bioinformatic analysis are needed.
Authors
- A. Nazlı Başak (ORCID: https://orcid.org/0000-0001-6977-2517)
- Roland Dominic G. Jamora (ORCID: https://orcid.org/0000-0001-5317-7369)
- Gerard Saranza (ORCID: https://orcid.org/0000-0001-8322-4226)
- Theresa Lüth (ORCID: https://orcid.org/0000-0003-0458-0498)
- Carolin Gabbert (ORCID: https://orcid.org/0000-0002-2308-9330)
- Elisabeth Stögmann (ORCID: https://orcid.org/0000-0003-4688-8482)
- Alexander Balck (ORCID: https://orcid.org/0000-0003-3967-0282)
- Cid Czarina E. Diesta (ORCID: https://orcid.org/0000-0003-3068-1065)
- Susen Schaake (ORCID: https://orcid.org/0009-0006-6021-3069)
- Christoph Much
- Philip Seibler (ORCID: https://orcid.org/0000-0002-3496-7194)
- Teresa Kleinz (ORCID: https://orcid.org/0009-0000-6313-7395)
- Max Borsche (ORCID: https://orcid.org/0000-0002-9651-5986)
- Joshua Laβ
- Tuğçe Gül (ORCID: https://orcid.org/0000-0002-1818-9839)
- Norbert Brüggemann (ORCID: https://orcid.org/0000-0001-5969-6899)
- Theresa König (ORCID: https://orcid.org/0000-0002-7904-8482)
- Raymond L. Rosales (ORCID: https://orcid.org/0000-0001-6387-1389)
- André Fienemann (ORCID: https://orcid.org/0009-0004-9594-3673)
- Julia C. Prietzsche
- Meret Möller
- Alexander Zimprich (ORCID: https://orcid.org/0000-0002-1668-5177)
- Christine Klein
- Joanne Trinh
- Christos Ganos
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2026-09-24
- DOI
- https://doi.org/10.1038/s41531-026-01585-4
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00