Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Rapid Targeted Sequencing Using Dried Blood Spot Samples for Patients With Suspected Actionable Genetic Diseases

  • Man Jin Kim (Department of Genomic Medicine, Seoul National University Hospital) ;
  • Soo Yeon Kim (Department of Genomic Medicine, Seoul National University Hospital) ;
  • Jin Sook Lee (Department of Pediatrics, Department of Genome Medicine and Science, Gil Medical Center, Gachon University College of Medicine) ;
  • Sanggoo Kang (MedySapiens, Inc.) ;
  • Lae-Jeong Park (Department of Electrical Engineering, Gangneung-Wonju National University) ;
  • Wooyong Choi (MedySapiens, Inc.) ;
  • Ju Yeol Jung (MedySapiens, Inc.) ;
  • Taehyung Kim (MedySapiens, Inc.) ;
  • Sung Sup Park (Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Jung Min Ko (Rare Disease Center, Seoul National University Hospital) ;
  • Moon-Woo Seong (Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Jong Hee Chae (Department of Genomic Medicine, Seoul National University Hospital)
  • Received : 2022.03.18
  • Accepted : 2022.11.16
  • Published : 2023.05.01
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Abstract

Background: New genome sequencing technologies with enhanced diagnostic efficiency have emerged. Rapid and timely diagnosis of treatable rare genetic diseases can alter their medical management and clinical course. However, multiple factors, including ethical issues, must be considered. We designed a targeted sequencing platform to avoid ethical issues and reduce the turnaround time. Methods: We designed an automated sequencing platform using dried blood spot samples and a NEOseq_ACTION panel comprising 254 genes associated with Mendelian diseases having curable or manageable treatment options. Retrospective validation was performed using data from 24 genetically and biochemically confirmed patients. Prospective validation was performed using data from 111 patients with suspected actionable genetic diseases. Results: In prospective clinical validation, 13.5% patients presented with medically actionable diseases, including short- or medium-chain acyl-CoA dehydrogenase deficiencies (N=6), hyperphenylalaninemia (N=2), mucopolysaccharidosis type IVA (N=1), alpha thalassemia (N=1), 3-methylcrotonyl-CoA carboxylase 2 deficiency (N=1), propionic acidemia (N=1), glycogen storage disease, type IX(a) (N=1), congenital myasthenic syndrome (N=1), and citrullinemia, type II (N=1). Using the automated analytic pipeline, the turnaround time from blood collection to result reporting was <4 days. Conclusions: This pilot study evaluated the possibility of rapid and timely diagnosis of treatable rare genetic diseases using a panel designed by a multidisciplinary team. The automated analytic pipeline maximized the clinical utility of rapid targeted sequencing for medically actionable genes, providing a strategy for appropriate and timely treatment of rare genetic diseases.

Keywords

Acknowledgement

This study was supported by the Technology Development Program (S2782642) funded by the Ministry of SMEs and Startups, Korea, and MedySapiens Inc.

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