NPJ Parkinson's disease · 2026
Unified long-read panel for Parkinson's and repeat expansion disorders.
СтатьяНазвание и аннотация: Перевод в очереди
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Fienemann André, Prietzsche Julia C, Laβ Joshua, Much Christoph, Schaake Susen, Lüth Theresa, Gabbert Carolin, Zimprich Alexander, Stögmann Elisabeth, König Theresa, Ganos Christos, Gül-Demirkale Tuğçe, Başak A Nazlı, Jamora Roland Dominic G, Rosales Raymond L, Saranza Gerard, Diesta Cid Czarina E, Möller Meret, Borsche Max, Kleinz Teresa, Balck Alexander, Brüggemann Norbert, Seibler Philip, Klein Christine, Trinh Joanne
Аннотация
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.