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Role of next generation sequencing in diagnosis and management of critically ill children with suspected monogenic disorder

European Journal of Human Genetics (2024)Cite this article

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Abstract

Next generation sequencing based diagnosis has emerged as a promising tool for evaluating critically ill neonates and children. However, there is limited data on its utility in developing countries. We assessed its diagnostic rate and clinical impact on management of pediatric patients with a suspected genetic disorder requiring critical care. The study was conducted at a single tertiary hospital in Northern India. We analyzed 70 children with an illness requiring intensive care and obtained a precise molecular diagnosis in 32 of 70 probands (45.3%) using diverse sequencing techniques such as clinical exome, whole exome, and whole genome. A significant change in clinical outcome was observed in 13 of 32 (40.6%) diagnosed probands with a change in medication in 11 subjects and redirection to palliative care in two subjects. Additional benefits included specific dietary management (three cases), avoidance of a major procedure (one case) and better reproductive counseling. Dramatic therapeutic responses were observed in three cases with SCN1A, SCN2A and KCNQ2-related epileptic encephalopathy. A delayed turn-around for sequencing results was perceived as a major limiting factor in the study, as rapid and ultra-rapid sequencing was not available. Achieving a precise molecular diagnosis has great utility in managing critically ill patients with suspected genetic disorders in developing countries.

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Fig. 1: NGS diagnostic yield as per patient phenotype and dataset analysis.
Fig. 2: Impact of diagnosis by NGS on outcome of 32 diagnosed cases.

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Data availability

The authors confirm that the data supporting the findings of the study are available within the article and its Supplementary Material. Raw data files will be made available on reasonable request.

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Acknowledgements

We would like to thank all the children and families who agreed to be part of this study.

Funding

The study was performed as part of clinical care without research funds.

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Authors and Affiliations

  1. Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India

    Sameer Bhatia, Swasti Pal, Samarth Kulshrestha, Renu Saxena, Sunita Bijarnia-Mahay, Ishwar Chander Verma & Ratna Dua Puri

  2. Department of Paediatrics, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India

    Dhiren Gupta

  3. Department of Neonatology, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India

    Arun Soni

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All the authors have made substantial contributions to the final manuscript including conception and design; acquisition, analysis or interpretation of data. Each author has participated sufficiently in the work and takes public responsibility for appropriate portions of the content. All the authors agree that they would be accountable for all aspects of the work to ensure that questions related to the integrity or accuracy of any part of the work are appropriately investigated and resolved. SB, ICV and RP made substantial contributions to conception and design. SB, DG, AS, SBM, ICV and RP contributed to acquisition of data. SB, SP, SK and RP contributed to analysis and interpretation of data. SB, SP, ICV and RP contributed in drafting the manuscript and critical revision. All authors approve the final version to be published.

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Correspondence to Ratna Dua Puri.

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The study was approved by the Institution Ethics Committee (EC/07/18/1384).

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Bhatia, S., Pal, S., Kulshrestha, S. et al. Role of next generation sequencing in diagnosis and management of critically ill children with suspected monogenic disorder. Eur J Hum Genet (2024). https://doi.org/10.1038/s41431-024-01569-z

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