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Clinical efficacy of a next-generation sequencing gene panel for primary immunodeficiency diagnostics

Clinical efficacy of a next-generation sequencing gene panel for primary immunodeficiency diagnostics
Clinical efficacy of a next-generation sequencing gene panel for primary immunodeficiency diagnostics
Primary immunodeficiencies (PIDs) are rare monogenic inborn errors of immunity that result in impairment of functions of the human immune system. PIDs have a broad phenotype with increased morbidity and mortality and treatment choices are often complex. With increased accessibility of next-generation sequencing the rate of discovery of genetic causes for PID has increased exponentially. Identification of an underlying monogenic diagnosis provides important clinical benefits for patients with the potential to alter treatments, facilitate genetic counselling, and pre-implantation diagnostics. We investigated a next-generation sequencing PID panel of 242 genes within clinical care across a range of PID phenotypes. We also evaluated Phenomizer to predict causal genes from human phenotype ontology (HPO) terms. 27 participants were recruited and a total of 15 reportable variants were identified in 48% (13/27) of the participants. The panel results had implications for treatment in 37% (10/27) of participants. Phenomizer identified the genes harbouring variants from HPO terms in 33% (9/27) of participants. This study demonstrates the clinical efficacy that genetic testing has in the care of PID. However, it also highlights some of the disadvantages of gene panels in the rapidly moving field of PID genomics and current challenges in HPO term assignment for PID.
0009-9163
Rae, William
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Ward, Daniel
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Mattocks, Christopher
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Pengelly, Reuben J.
af97c0c1-b568-415c-9f59-1823b65be76d
Eren, Efrem
ac449fc8-4ae2-4efd-ad91-9dcea3f355e2
Patel, Sanjay V.
3a22c83b-5edb-471c-997b-dbad703b6ede
Faust, Saul N.
f97df780-9f9b-418e-b349-7adf63e150c1
Hunt, David
5867549e-0e44-4f07-9a42-93aaf092fd4d
Williams, Anthony P.
973ff46f-46f1-4d7c-b27d-0f53221e4c44
Rae, William
8746e0ae-b868-4356-9c89-fe78600cf427
Ward, Daniel
8343934a-ac4c-4042-ad30-93270144f77d
Mattocks, Christopher
2d943111-cfdf-4f0d-9ecc-0737e541fe36
Pengelly, Reuben J.
af97c0c1-b568-415c-9f59-1823b65be76d
Eren, Efrem
ac449fc8-4ae2-4efd-ad91-9dcea3f355e2
Patel, Sanjay V.
3a22c83b-5edb-471c-997b-dbad703b6ede
Faust, Saul N.
f97df780-9f9b-418e-b349-7adf63e150c1
Hunt, David
5867549e-0e44-4f07-9a42-93aaf092fd4d
Williams, Anthony P.
973ff46f-46f1-4d7c-b27d-0f53221e4c44

Rae, William, Ward, Daniel, Mattocks, Christopher, Pengelly, Reuben J., Eren, Efrem, Patel, Sanjay V., Faust, Saul N., Hunt, David and Williams, Anthony P. (2017) Clinical efficacy of a next-generation sequencing gene panel for primary immunodeficiency diagnostics. Clinical Genetics. (doi:10.1111/cge.13163).

Record type: Article

Abstract

Primary immunodeficiencies (PIDs) are rare monogenic inborn errors of immunity that result in impairment of functions of the human immune system. PIDs have a broad phenotype with increased morbidity and mortality and treatment choices are often complex. With increased accessibility of next-generation sequencing the rate of discovery of genetic causes for PID has increased exponentially. Identification of an underlying monogenic diagnosis provides important clinical benefits for patients with the potential to alter treatments, facilitate genetic counselling, and pre-implantation diagnostics. We investigated a next-generation sequencing PID panel of 242 genes within clinical care across a range of PID phenotypes. We also evaluated Phenomizer to predict causal genes from human phenotype ontology (HPO) terms. 27 participants were recruited and a total of 15 reportable variants were identified in 48% (13/27) of the participants. The panel results had implications for treatment in 37% (10/27) of participants. Phenomizer identified the genes harbouring variants from HPO terms in 33% (9/27) of participants. This study demonstrates the clinical efficacy that genetic testing has in the care of PID. However, it also highlights some of the disadvantages of gene panels in the rapidly moving field of PID genomics and current challenges in HPO term assignment for PID.

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Rae_et_al-2017-Clinical_Genetics - Accepted Manuscript
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Accepted/In Press date: 23 October 2017
e-pub ahead of print date: 27 October 2017

Identifiers

Local EPrints ID: 415578
URI: https://eprints.soton.ac.uk/id/eprint/415578
ISSN: 0009-9163
PURE UUID: d50bbcb7-d4e3-4623-b822-ea579106f7a2
ORCID for Reuben J. Pengelly: ORCID iD orcid.org/0000-0001-7022-645X
ORCID for Saul N. Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 15 Nov 2017 17:30
Last modified: 03 Dec 2019 05:44

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Contributors

Author: William Rae
Author: Daniel Ward
Author: Christopher Mattocks
Author: Efrem Eren
Author: Sanjay V. Patel
Author: Saul N. Faust ORCID iD
Author: David Hunt

University divisions

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