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Original research
Genetic landscape of congenital disorders in patients from Southeast Asia: results from sequencing using a gene panel for Mendelian phenotypes
  1. Heming Wei1,
  2. Angeline Lai2,3,
  3. Ee Shien Tan2,3,
  4. Mark Jean Aan Koh2,4,
  5. Ivy Ng2,5,
  6. Teck Wah Ting2,5,
  7. Terrence Thomas2,6,
  8. Breana Cham3,
  9. Jiin Ying Lim3,
  10. Sylvia Kam3,
  11. Chew Yin Jasmine Goh3,
  12. Grace Lin1,
  13. Maggie Brett1,
  14. Derrick Chan2,6,
  15. Saumya Shekhar Jamuar2,3,
  16. Ene-Choo Tan1,2
  1. 1 KK Research Centre, KK Women's & Children's Hospital, Singapore
  2. 2 Paediatric Academic Clinical Programme, SingHealth Duke-NUS Graduate Medical School, Singapore
  3. 3 Genetics Service, KK Women's & Children's Hospital, Singapore
  4. 4 Dermatology Service, KK Women's & Children's Hospital, Singapore
  5. 5 Genetics Service, KK Women's and Children's Hospital, Singapore
  6. 6 Neurology Service, KK Women's & Children's Hospital, Singapore
  1. Correspondence to Ene-Choo Tan, KK Research Centre, KK Women's and Children's Hospital, Singapore 229899, Singapore; tan.ene.choo{at}kkh.com.sg

Abstract

Objective To test the utility and diagnostic yield of a medical-exome gene panel for identifying pathogenic variants in Mendelian disorders.

Methods Next-generation sequencing was performed with the TruSight One gene panel (targeting 4813 genes) followed by MiSeq sequencing on 216 patients who presented with suspected genetic disorders as assessed by their attending physicians.

Results There were 56 pathogenic and 36 likely pathogenic variants across 57 genes identified in 87 patients. Causal mutations were more likely to be truncating and from patients with a prior clinical diagnosis. Another 18 promising variants need further evaluation for more evidence to meet the requirement for potential upgrade to pathogenic. Forty-five of the 92 clinically significant variants were novel.

Conclusion The 40.3% positive yield compares favourably with similar studies using either this panel or whole exome sequencing, demonstrating that large gene panels could be a good alternative to whole exome sequencing for quick genetic confirmation of Mendelian disorders.

  • genetics
  • syndrome
  • molecular biology

https://doi.org/10.1136/archdischild-2020-319177

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    Footnotes

    • Contributors HW: data analysis, drafting of manuscript. AL: patient assessment and recruitment, data analysis. EST: patient assessment and recruitment, data analysis. MJAK: patient assessment and recruitment, data analysis. IN: patient assessment and recruitment, data analysis. TWT: patient assessment and recruitment, data analysis. TT: patient assessment and recruitment, data analysis. BC: patient assessment and recruitment, genetic counselling. JYL: patient assessment and recruitment, genetic counselling. SK: patient assessment and recruitment, genetic counselling. CYJG: patient assessment and recruitment, genetic counselling. GL: data analysis. MB: data analysis. DC: patient assessment and recruitment, data analysis. SSJ: patient assessment and recruitment, data analysis. ECT: funding support, supervision, data analysis, manuscript writing.

    • Funding Supported by grants 02/FY2016/P1/03-A14 from the SingHealth Duke-NUS Academic Medical Centre, and NMRC/CG/006/2013 and NMRC/CG/M003/2017 from the Singapore Ministry of Health’s National Medical Research Council.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data will be available on request from the corresponding author.

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