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IRC-SET 2018 pp 263-273 | Cite as

Resolving the Diagnostic Odyssey of a Patient with an Undefined Neuromuscular Disorder Using Massively Parallel Sequencing Approaches

  • Yu Yiliu
  • Ong Hui JuanEmail author
  • Swati Tomar
  • Grace Tan Li Xuan
  • Raman Sethi
  • Tay Kiat Hong
  • Lai Poh San
Conference paper

Abstract

We investigated the effectiveness of DNA-based next-generation sequencing (NGS) targeting different genomic region and coverage from five platforms in resolving the diagnostic odyssey of a patient with an unidentified neuromuscular disorder. There were advantages and limitations associated with the different platform approaches. On average, over 22,000 rare protein effecting single nucleotide variants (SNVs), 1955 structural variants (SVs), and 229 copy number variants (CNVs) were identified and analyzed. Seven candidate SNVs fulfilled filtration criteria but were likely to be non-causative due to their classification or disease phenotype. Assessment of an intronic event through IGV and PCR suggested a region of structural rearrangement in DMD gene, which mismatched to two other genes on chromosome X hinting towards a possible novel mechanism of gene inactivation. Our results show that NGS platforms detect candidate variants but some disease mechanisms may remain undetected and points for need for caution when applying NGS for diagnostic purposes.

Keywords

Next generation sequencing Targeted sequencing Whole exome sequencing Whole genome sequencing Neuromuscular disorder 

Notes

Acknowledgements

We would like to thank our mentors: Professor Lai Poh San, Dr. Swati Tomar, Ms. Grace Tan, Mr. Raman and Mr. Tay Kiat Hong for their invaluable guidance and help throughout the entire course of the project.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Yu Yiliu
    • 1
  • Ong Hui Juan
    • 1
    Email author
  • Swati Tomar
    • 2
  • Grace Tan Li Xuan
    • 2
  • Raman Sethi
    • 2
  • Tay Kiat Hong
    • 2
  • Lai Poh San
    • 2
  1. 1.Raffles InstitutionSingaporeSingapore
  2. 2.Department of Paediatrics, YYL School of MedicineNational University of SingaporeSingaporeSingapore

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