Severe X-linked chronic granulomatous disease in two unrelated females

Chollet‐Martin, Sylvie; Lopez, Anne; Gaud, C.; Henry, Dominique; Stos, Bertrand; Benna, Jamel El; Chedevile, Gaëlle; Gendrel, D.; Gougerot‐Pocidalo, Marie‐Anne; Grandchamp, Bernard; Gérard, Bénédicte

doi:10.1007/s00431-006-0211-3

Cited by 19 publications

(8 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Carrier-status with a CYBB gene defect being secondary to an extremely skewed X-inactivation event is rare (<2% of all reported CGD cases), but has been observed [18; 25; 51; 52; 53; 54]. Initial presentation of the CGD phenotype typically occurs in childhood, however several cases involving CGD carriers appear later in life, suggesting the possibility of a shift in X-inactivation with age [18; 53; 54].…”

Section: Discussionmentioning

confidence: 99%

X-linked chronic granulomatous disease secondary to skewed X chromosome inactivation in a female with a novel CYBB mutation and late presentation

Lewis

Singla

Sergeant

et al. 2008

Clinical Immunology

View full text Add to dashboard Cite

Chronic Granulomatous Disease (CGD) is characterized by defects in the superoxide producing enzyme NADPH oxidase causing phagocytes to improperly clear invading pathogens. Here we report findings of a late presenting 16 year old female with X-linked CGD. The patient presented with community-acquired pneumonia, but symptoms persisted for 2 weeks during triple antimicrobial coverage. Cultures revealed Aspergillus fumigatus which was resolved through aggressive voriconazole treatment. Neutrophil studies revealed NADPH oxidase activity and flavocytochrome b 558 levels that were 4-8% of controls and suggested carrier status of the mother. We found a null mutation in the CYBB gene (c.252insAG) predicting an aberrant gp91 phox protein (p.Cys85fsX23) in the heterozygous state. Methylation analysis demonstrated extremely skewed X chromosome inactivation favoring the maternally inherited defective gene. In conclusion, a novel mutation in the CYBB gene and an extremely skewed X-inactivation event resulted in the rare expression of the CGD phenotype in a carrier female.

show abstract

Section: Discussionmentioning

confidence: 99%

X-linked chronic granulomatous disease secondary to skewed X chromosome inactivation in a female with a novel CYBB mutation and late presentation

Lewis

Singla

Sergeant

et al. 2008

Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…PCR products were purified (QIAquick gel extraction kit; QIAGEN), and both strands were sequenced with the use of fluorescent ddNTPs (BigDye) on an ABI Prism 3130XL Genetic Analyzer (Biosystems) and analyzed with ABI PRISM GeneMapper software version 3.0. Analysis of Xchromosome inactivation was performed as previously described 20 with the use of the androgen receptor polymorphism as a marker.…”

Section: Dna Analysismentioning

confidence: 99%

ALAS2 acts as a modifier gene in patients with congenital erythropoietic porphyria

To‐Figueras

Ducamp

Clayton

et al. 2011

Blood

View full text Add to dashboard Cite

Mutations in the uroporphyrinogen III synthase (UROS) gene cause congenital erythropoietic porphyria (CEP), an autosomalrecessive inborn error of erythroid heme biosynthesis. Clinical features of CEP include dermatologic and hematologic abnormalities of variable severity. The discovery of a new type of erythroid porphyria, X-linked dominant protoporphyria (XLDPP), which results from increased activity of 5-aminolevulinate synthase 2 (ALAS2), the rate-controlling enzyme of erythroid heme synthesis, led us to hypothesize that the CEP phenotype may be modulated by sequence variations in the ALAS2 gene. We genotyped ALAS2 in 4 unrelated CEP patients exhibiting the same C73R/P248Q UROS genotype. The most severe of the CEP patients, a young girl, proved to be heterozygous for a novel ALAS2 mutation: c.1757 A > T in exon 11. This mutation is predicted to affect the highly conserved and penultimate C-terminal amino acid of ALAS2 (Y586). The rate of 5-aminolevulinate release from Y586F was significantly increased over that of wild-type ALAS2. The contribution of the ALAS2 gain-of-function mutation to the CEP phenotype underscores the importance of modifier genes underlying CEP. We propose that ALAS2 gene mutations should be considered not only as causative of X-linked sideroblastic anemia (XLSA) and XLDPP but may also modulate gene function in other erythropoietic

show abstract

“…Biological diagnosis of CGD was based on determining the PMN respiratory burst by chemiluminescence, nitroblue tetrazolium reduction assay (NBT test) and flow cytometric dichlorofluorescein (DCFH) assay, as previously described (Gérard et al, 2001;Chollet-Martin et al, 2007). Reactive oxygen species (ROS) were quantified by chemiluminescence after PMA stimulation (units: count per minute/10 6 PMN; normal range: >10 6 ).…”

Section: Functional and Phenotype Analysis Of Polymorphonuclear Neutrmentioning

confidence: 99%

“…In order to diagnose carrier females, several investigations of functional subpopulations were done using the NBT test in the presence of endotoxin (LPS, Escherichia coli O 55:B5) or Staphylococcus epidermidis (10 7 CFU/ml) (results are expressed as % of cells testing positive, normal range: 75-100, as determined from 30 healthy individuals) and the flow cytometric DCFH assay (results are expressed as mean of the fluorescence intensity of DCF in the resting state and after PMA stimulation (range in the resting state: 10 -20; range after PMA stimulation: 100 -200). Immunoblotting of the various NADPH oxidase components (gp91phox, p22phox, p67phox and p47phox) was performed as previously described (El Benna et al, 1999 ;Chollet-Martin et al, 2007).Polyclonal rabbit anti-E134 Kannengiesser et algp91phox antibody (directed against a C-terminal sequence) was from Upstate Biotechnology, polyclonal rabbit anti-p22phox antibody (directed against whole p22phox) was from Santa Cruz, and polyclonal rabbit anti-p47phox and -p67phox antibodies (both directed against a C-terminal sequence) were a gift from Dr Babior (The Scripps Research institute, CA, USA). …”

mentioning

confidence: 99%

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

et al. 2008

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Severe X-linked chronic granulomatous disease in two unrelated females

Cited by 19 publications

References 22 publications

X-linked chronic granulomatous disease secondary to skewed X chromosome inactivation in a female with a novel CYBB mutation and late presentation

X-linked chronic granulomatous disease secondary to skewed X chromosome inactivation in a female with a novel CYBB mutation and late presentation

ALAS2 acts as a modifier gene in patients with congenital erythropoietic porphyria

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

Contact Info

Product

Resources

About