Molecular epidemiology of chronic granulomatous disease in a series of 80 kindreds: identification of 31 novel mutations.
Chronic granulomatous disease (CGD) results from constitutional inactivating mutations in the CYBB, NCF1, CYBA or NCF2 genes that encode subunits of phagocyte NADPH oxidase. We report the findings of molecular analysis of 80 kindred. In 75 unrelated male and 5 female probands, CGD was suspected on the basis of clinical symptoms, and biological samples were referred to our laboratory between 2000 and 2007. Seventy seven patients were found to have mutations in CYBB, NCF1, CYBA or NCF2 (52 different mutations including 31 mutations not previously reported). CYBB was the most frequently mutated gene (58 males and 3 females, 76%). In autosomal recessive forms of the disease, mutations were found in NCF1 (11 patients), NCF2 (3 patients) and CYBA (2 patients). We observed that significantly fewer females were affected by autosomal recessive CGD than expected (2 females/14 males; p=0.002), suggesting that female patients with CGD may be under diagnosed.
AP-HP, Hôpital Bichat-Claude Bernard, Service de Biochimie Hormonale et Génétique, 46 rue Henri Huchard, 75018 Paris, France.
Caroline
C
Kannengiesser
Bénédicte
B
Gérard
Jamel
J
El Benna
Dominique
D
Henri
Yolande
Y
Kroviarski
Sylvie
S
Chollet-Martin
Marie-Anne
MA
Gougerot-Pocidalo
Carole
C
Elbim
Bernard
B
Grandchamp
D005192:Family Health; D005260:Female; D005786:Gene Expression Regulation; D005808:Genes, Recessive; D006105:Granulomatous Disease, Chronic / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D017720:Molecular Epidemiology; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D010586:Phagocytes / Q000201:enzymology*; D010641:Phenotype
D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C086986:CYBA protein, human; C527764:NCF2 protein, human; C060505:neutrophil cytosolic factor 1