Collaborative studies involving group in Canada and the USA have identified a new genetic subgroup of autosomal recessive CGD. The gene defect has been found is a gene called NCF4 that codes for part of the oxidase enzyme complex, p40phox, not previously reported as a cause of CGD.
The work, headed by Professor Dinauer of the Indiana School of Medicine with Dr Nicola Wright and colleagues at the Alberta Children's Hospital and University of Calgary and Professor Nauseef of the University of Iowa, has implications for diagnosing autosomal recessive CGD in people who suffer form gastrointestinal problems.
Professor Dinauer explains 'We know that superoxide production by the white blood cells involves six components of the NADPH oxidase enzyme working together. To date CGD has been associated with mutations in four of the major subunits that make up this enzyme. We have now identified a mutation in the NCF4 gene that encodes for the p40 phox subunit in a patient who was suffering from granulomatous colitis.'
In the work published in the journal 'Blood' the authors believe that this autosomal defect in the NCF4 gene should be classified as a fifth genetic subgroup of CGD.
'The role of p40phox as part of the oxidase complex has been poorly understood until recently but we can now add new information that a genetic mutation in this subunit can cause gastrointestinal symptoms of CGD and an inability to fight off infections. Exploring the role of the p40phox subunit and the NADPH oxidase in inflammatory bowel disease and immune processes will be a key priority in the future', said Professor Dinauer.
'I believe this study has informed us on a number of important areas', adds Professor Nauseef. 'In some patients gastrointestinal problems can be the presenting or only manifestations of CGD, We have now found a link between this gene, NCF4, its effects on the production of oxidants within the cell and granulomatous colitis. This finding will make it possible for paediatric gastro-enterologists to more accurately identify patients with CGD.'
Publication
A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40phox and selective defects in Neutrophil NADPH oxidase activity. Blood. 2009 Aug 19.
Matute JD, Arias AA, Wright NA, Wrobel I, Waterhouse CC, Li XJ, Marchal CC, Stull ND, Lewis DB, Steele M, Kellner JD, Yu W, Meroueh SO, Nauseef WM, Dinaeur MC.
IMPORTANT NOTE :
The information contained on this website is intended only as a guideline, not as a substitute for medical advice. Always consult your doctor if you or your child has any CGD symptoms or concerns.
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