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Rapid and comprehensive diagnostic method for repeat expansion diseases using nanopore sequencing.

Satoko MiyatakeEriko KoshimizuAtsushi FujitaHiroshi DoiMasaki OkuboTaishi WadaKohei HamanakaNaohisa UedaHitaru KishidaGaku MinaseAtsuhiro MatsunoMinori KodairaKatsuhisa OgataRumiko KatoAtsuhiko SugiyamaAyako SasakiTakabumi MiyamaMai SatohYuri UchiyamaNaomi TsuchidaHaruka HamanoueKazuharu MisawaKiyoshi HayasakaYoshiki SekijimaHiroaki AdachiKunihiro YoshidaFumiaki TanakaTakeshi MizuguchiNaomichi Matsumoto
Published in: NPJ genomic medicine (2022)
We developed a diagnostic method for repeat expansion diseases using a long-read sequencer to improve currently available, low throughput diagnostic methods. We employed the real-time target enrichment system of the nanopore GridION sequencer using the adaptive sampling option, in which software-based target assignment is available without prior sample enrichment, and built an analysis pipeline that prioritized the disease-causing loci. Twenty-two patients with various neurological and neuromuscular diseases, including 12 with genetically diagnosed repeat expansion diseases and 10 manifesting cerebellar ataxia, but without genetic diagnosis, were analyzed. We first sequenced the 12 molecularly diagnosed patients and accurately confirmed expanded repeats in all with uniform depth of coverage across the loci. Next, we applied our method and a conventional method to 10 molecularly undiagnosed patients. Our method corrected inaccurate diagnoses of two patients by the conventional method. Our method is superior to conventional diagnostic methods in terms of speed, accuracy, and comprehensiveness.
Keyphrases
  • end stage renal disease
  • ejection fraction
  • newly diagnosed
  • chronic kidney disease
  • peritoneal dialysis
  • prognostic factors
  • genome wide
  • healthcare
  • single cell
  • patient reported
  • subarachnoid hemorrhage