Parkinson için birleşik uzun okuma paneli ve tekrar genişleme bozuklukları.

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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.

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