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Utility of Next Generation Sequencing in Clinical Primary Immunodeficiencies

Abstract

Primary immunodeficiencies (PIDs) are a group of genetically heterogeneous disorders that present with very similar symptoms, complicating definitive diagnosis. More than 240 genes have hitherto been associated with PIDs, of which more than 30 have been identified in the last 3 years. Next generation sequencing (NGS) of genomes or exomes of informative families has played a central role in the discovery of novel PID genes. Furthermore, NGS has the potential to transform clinical molecular testing for established PIDs, allowing all PID differential diagnoses to be tested at once, leading to increased diagnostic yield, while decreasing both the time and cost of obtaining a molecular diagnosis. Given that treatment of PID varies by disease gene, early achievement of a molecular diagnosis is likely to enhance treatment decisions and improve patient outcomes.

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Acknowledgments

The project was supported in part by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number KL2 TR000089 to Darrell L. Dinwiddie, PhD. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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Nikita Raje, Sarah Soden, Christina E. Ciaccio, and Stephen F. Kingsmore declare no conflict of interest. Douglas Swanson declares grants from Pfizer, Inc., outside the submitted work.

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This article does not contain any studies with human or animal subjects performed by any authors.

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Correspondence to Nikita Raje.

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This article is part of the Topical Collection on Pediatric Allergy and Immunology

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Raje, N., Soden, S., Swanson, D. et al. Utility of Next Generation Sequencing in Clinical Primary Immunodeficiencies. Curr Allergy Asthma Rep 14, 468 (2014). https://doi.org/10.1007/s11882-014-0468-y

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Keywords

  • Whole genome sequencing
  • Whole exome sequencing
  • Primary immunodeficiency
  • Next generation sequencing
  • Single nucleotide variation
  • Single nucleotide polymorphism