Severe phenotype of chronic granulomatous disease presenting in a female with a de novo mutation in gp91-phox and a non familial, extremely skewed X chromosome inactivation

Anderson-Cohen, Mindy; Holland, Steve; Kuhns, Doug B; Fleisher, Thomas A.; Ding, Li; Brenner, Sebastian; Malech, Harry L.; Roesler, Joachim

doi:10.1016/j.clim.2003.08.002

Cited by 70 publications

(34 citation statements)

References 50 publications

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“…The CYBB gene is located on the X chromosome, whereas all other components are inherited in an autosomal mode. Female carriers normally have two subsets of PMNs in their peripheral blood due to random X chromosome inactivation (lyonization): one subset is functionally normal, whereas the other is defective (25). These subpopulations are easily detected by oxidation of DCFH after stimulation of isolated PMNs with phorbol-myristate-acetate.…”

Section: Identification Of Pmn Functional Subpopulations Using Flow Cmentioning

confidence: 99%

Flow cytometric investigation of neutrophil oxidative burst and apoptosis in physiological and pathological situations

Elbim

Lizard

2009

Cytometry Pt A

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Flow cytometric analysis provides a rapid screen for abnormalities of polymorphonuclear neutrophils (PMN) function and reflect their behavior in vivo more accurately. This review summarizes the major fluorescent probes used to study PMN oxidative burst and apoptosis using flow cytometry (FCM). We also provide examples of FCM studies in physiological and pathological situations, illustrating the advantages of FCM for assessment of PMN oxidative burst and PMN apoptosis. These data point to the role of FCM in detecting primary immunodeficiencies such as IRAK4 deficiency and support the use of the assessment of the PMN oxidative burst for routine testing in patients with bacterial infections. We also demonstrate the utility of whole-blood analysis using FCM for a better understanding of PMN functionality, i.e., tuning PMN responses to inflammatory stimuli. Finally, FCM permits a simultaneous analysis of phenotypic, functional and morphometric parameters assessing whole-blood PMN apoptosis, in particular in response to Toll-like receptor agonists and during simian immunodeficiency virus infection. '

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Section: Identification Of Pmn Functional Subpopulations Using Flow Cmentioning

confidence: 99%

Flow cytometric investigation of neutrophil oxidative burst and apoptosis in physiological and pathological situations

Elbim

Lizard

2009

Cytometry Pt A

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“…Interestingly, all three mutations identified in females affected by severe X-linked chronic granulomatous disease in our series were de novo mutations. One other report pointed out that a female affected by X linked CGD was carrier of a de novo mutation (Anderson-Cohen et al, 2003). Other symptomatic female carriers have been described in case reports, but often without specifying whether they had a de novo or inherited mutation (Cazzola et al, 1985;Romera-Modamio et al, 1997;Rosen-Wolff et al, 2001;Lun et al, 2002).…”

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confidence: 93%

Molecular epidemiology of chronic granulomatous disease in a series of 80 kindreds: identification of 31 novel mutations

et al. 2008

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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.

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“…For instance, Uhlemann et al [2004] have reported an association between microsatellite alleles in the promoter region of CYBB and severity of malaria in Gabon populations, and correlative in vitro experiments suggest that these alleles could be associated with differences in NADPH oxidase activity. Skewed lyonization in female carriers of CYBB mutations is known to be associated with higher susceptibility to autoimmune diseases [Anderson-Cohen et al, 2003]. Moreover, Roos et al [2003] have postulated that an imbalance in products of the respiratory burst could produce tissue damage in a range of diseases, such as gout, chronic obstructive pulmonary disease, rheumatoid arthritis, and also may be involved in the pathogenesis of cardiovascular diseases [Brandes and Kreuzer, 2005].…”

Section: Introductionmentioning

confidence: 99%

CYBB, an NADPH-oxidase gene: restricted diversity in humans and evidence for differential long-term purifying selection on transmembrane and cytosolic domains

Tarazona‐Santos¹,

Bernig²,

Burdett³

et al. 2008

Hum. Mutat.

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CYBB encodes the gp91-phox protein of the phagocytic NADPH oxidase; the innate immunity-related enzymatic complex responsible for the respiratory burst. Mutations in CYBB can cause chronic granulomatous disease (CGD), a primary immunodeficiency characterized by ineffective microbicidal activity, for which over 150 family-specific mutations have been described. It is also plausible that common SNPs in CYBB alter the expression or function of gp91-phox, determining differences in susceptibility to complex disorders such as autoimmune or infectious diseases. We have resequenced the exons, UTRs, and intronic regions of CYBB in 102 ethnically diverse individuals and genotyped nine tag-SNPs in 942 individuals from 52 worldwide populations. The 28 observed SNPs (none of which nonsynonymous) reside on 28 haplotypes that can be collapsed into five clades. CYBB shows lower diversity than other X-chromosome genes and most of the between-population genetic variance was observed among Africans and non-Africans. The African population shows the highest diversity and the lowest linkage disequilibrium (LD). Because there is extensive shared LD among non-Africans, tag-SNPs can be effectively employed in gene-centric association studies and are portable across Eurasian and Native American populations. Comparison of CYBB coding sequences among mammals evidences the action of long-term purifying selection, which is stronger on the C-terminal cytosolic domain than on the N-terminal transmembrane domain of gp91-phox.

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Severe phenotype of chronic granulomatous disease presenting in a female with a de novo mutation in gp91-phox and a non familial, extremely skewed X chromosome inactivation

Cited by 70 publications

References 50 publications

Flow cytometric investigation of neutrophil oxidative burst and apoptosis in physiological and pathological situations

Flow cytometric investigation of neutrophil oxidative burst and apoptosis in physiological and pathological situations

Molecular epidemiology of chronic granulomatous disease in a series of 80 kindreds: identification of 31 novel mutations

CYBB, an NADPH-oxidase gene: restricted diversity in humans and evidence for differential long-term purifying selection on transmembrane and cytosolic domains

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