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Novel Diagnostic Tool for p47 -Deficient Chronic Granulomatous Disease Patient and Carrier Detection


Wrona, Dominik; Siler, Ulrich; Reichenbach, Janine (2019). Novel Diagnostic Tool for p47 -Deficient Chronic Granulomatous Disease Patient and Carrier Detection. Molecular Therapy - Methods & Clinical Development, 13:274-278.

Abstract

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations of the phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Autosomal recessive p47 -deficient CGD (p47 CGD) is the second most frequent form of the disease in western countries, and more than 94% of patients have a disease-causing dinucleotide deletion (ΔGT) in the neutrophil cytosolic factor 1 () gene. The ΔGT mutation is most likely transferred onto the from one of its two pseudogenes co-localized on the same chromosome. The presence of pseudogenes in healthy individuals makes the genetic diagnostics of ΔGT p47 CGD challenging, as it requires the distinction between ΔGT in and in the two pseudogenes. We have developed a diagnostic tool for the identification of p47 CGD based on PCR co-amplification of and its pseudogenes, followed by band intensity quantification of restriction fragment length polymorphism products. The single-day, reliable p47 CGD diagnostics allow for robust discrimination of homozygous ΔGT p47 CGD patients from heterozygous carriers and healthy individuals, as well as for monitoring gene therapy efficacy.

Abstract

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations of the phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Autosomal recessive p47 -deficient CGD (p47 CGD) is the second most frequent form of the disease in western countries, and more than 94% of patients have a disease-causing dinucleotide deletion (ΔGT) in the neutrophil cytosolic factor 1 () gene. The ΔGT mutation is most likely transferred onto the from one of its two pseudogenes co-localized on the same chromosome. The presence of pseudogenes in healthy individuals makes the genetic diagnostics of ΔGT p47 CGD challenging, as it requires the distinction between ΔGT in and in the two pseudogenes. We have developed a diagnostic tool for the identification of p47 CGD based on PCR co-amplification of and its pseudogenes, followed by band intensity quantification of restriction fragment length polymorphism products. The single-day, reliable p47 CGD diagnostics allow for robust discrimination of homozygous ΔGT p47 CGD patients from heterozygous carriers and healthy individuals, as well as for monitoring gene therapy efficacy.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:14 June 2019
Deposited On:31 Jul 2019 11:44
Last Modified:27 Feb 2020 08:31
Publisher:Cell Press (Elsevier)
ISSN:2329-0501
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.omtm.2019.02.001
PubMed ID:30859112

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