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

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IRC-SET 2018

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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.

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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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Authors and Affiliations

  1. Raffles Institution, Singapore, Singapore

    Yu Yiliu & Ong Hui Juan

  2. Department of Paediatrics, YYL School of Medicine, National University of Singapore, Singapore, Singapore

    Swati Tomar, Grace Tan Li Xuan, Raman Sethi, Tay Kiat Hong & Lai Poh San

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  1. Yu Yiliu
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  2. Ong Hui Juan
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  3. Swati Tomar
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  4. Grace Tan Li Xuan
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  7. Lai Poh San
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Corresponding author

Correspondence to Ong Hui Juan .

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Editors and Affiliations

  1. Institute for Infocomm Research (I²R), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore

    Huaqun Guo

  2. National University of Singapore, Singapore, Singapore

    Hongliang Ren

  3. Singapore Institute for Neurotechnology, National University of Singapore, Singapore, Singapore

    Aishwarya Bandla

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Yiliu, Y. et al. (2019). Resolving the Diagnostic Odyssey of a Patient with an Undefined Neuromuscular Disorder Using Massively Parallel Sequencing Approaches. In: Guo, H., Ren, H., Bandla, A. (eds) IRC-SET 2018. Springer, Singapore. https://doi.org/10.1007/978-981-32-9828-6_22

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