Diagnosis of chronic granulomatous disease: strengths and challenges in the Genomic Era

Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. Despite recent advances in our understanding of the genetic and...

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Main Authors: O’Donovan, Conor J., Tan, Lay Teng, Z. Abidin, Mohd A., Roderick, Marion R., Grammatikos, Alexandros, Bernatoniene, Jolanta
Format: Article
Language:English
Published: Multidisciplinary Digital Publishing Institute 2024
Online Access:http://psasir.upm.edu.my/id/eprint/116725/
http://psasir.upm.edu.my/id/eprint/116725/1/116725.pdf
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author O’Donovan, Conor J.
Tan, Lay Teng
Z. Abidin, Mohd A.
Roderick, Marion R.
Grammatikos, Alexandros
Bernatoniene, Jolanta
author_facet O’Donovan, Conor J.
Tan, Lay Teng
Z. Abidin, Mohd A.
Roderick, Marion R.
Grammatikos, Alexandros
Bernatoniene, Jolanta
author_sort O’Donovan, Conor J.
building UPM Institutional Repository
collection Online Access
description Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. In the current review, we provide an up-to-date summary of CGD pathophysiology, underpinning current methods of diagnostic testing for CGD and closely related disorders. We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. We discuss current and historical methods for functional testing of NADPH oxidase activity, as well as assays for measuring protein expression of NADPH oxidase subunits. Lastly, we focus on genetic and genomic methods employed to diagnose CGD, including gene-targeted panels, comprehensive genomic testing and ancillary methods. Throughout, we highlight general limitations of testing, and caveats specific to interpretation of results in the context of CGD and related disorders, and provide an outlook for newborn screening and the future.
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spelling upm-1167252025-04-15T06:45:53Z http://psasir.upm.edu.my/id/eprint/116725/ Diagnosis of chronic granulomatous disease: strengths and challenges in the Genomic Era O’Donovan, Conor J. Tan, Lay Teng Z. Abidin, Mohd A. Roderick, Marion R. Grammatikos, Alexandros Bernatoniene, Jolanta Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. In the current review, we provide an up-to-date summary of CGD pathophysiology, underpinning current methods of diagnostic testing for CGD and closely related disorders. We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. We discuss current and historical methods for functional testing of NADPH oxidase activity, as well as assays for measuring protein expression of NADPH oxidase subunits. Lastly, we focus on genetic and genomic methods employed to diagnose CGD, including gene-targeted panels, comprehensive genomic testing and ancillary methods. Throughout, we highlight general limitations of testing, and caveats specific to interpretation of results in the context of CGD and related disorders, and provide an outlook for newborn screening and the future. Multidisciplinary Digital Publishing Institute 2024-07-29 Article PeerReviewed text en cc_by_4 http://psasir.upm.edu.my/id/eprint/116725/1/116725.pdf O’Donovan, Conor J. and Tan, Lay Teng and Z. Abidin, Mohd A. and Roderick, Marion R. and Grammatikos, Alexandros and Bernatoniene, Jolanta (2024) Diagnosis of chronic granulomatous disease: strengths and challenges in the Genomic Era. Journal of Clinical Medicine, 13 (15). art. no. 4435. pp. 1-25. ISSN 2077-0383 https://www.mdpi.com/2077-0383/13/15/4435 10.3390/jcm13154435
spellingShingle O’Donovan, Conor J.
Tan, Lay Teng
Z. Abidin, Mohd A.
Roderick, Marion R.
Grammatikos, Alexandros
Bernatoniene, Jolanta
Diagnosis of chronic granulomatous disease: strengths and challenges in the Genomic Era
title Diagnosis of chronic granulomatous disease: strengths and challenges in the Genomic Era
title_full Diagnosis of chronic granulomatous disease: strengths and challenges in the Genomic Era
title_fullStr Diagnosis of chronic granulomatous disease: strengths and challenges in the Genomic Era
title_full_unstemmed Diagnosis of chronic granulomatous disease: strengths and challenges in the Genomic Era
title_short Diagnosis of chronic granulomatous disease: strengths and challenges in the Genomic Era
title_sort diagnosis of chronic granulomatous disease: strengths and challenges in the genomic era
url http://psasir.upm.edu.my/id/eprint/116725/
http://psasir.upm.edu.my/id/eprint/116725/
http://psasir.upm.edu.my/id/eprint/116725/
http://psasir.upm.edu.my/id/eprint/116725/1/116725.pdf