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Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder more common in autosomal recessive (AR) than X-linked in Iran. This study aimed to assess whether having a child with AR-CGD would increase the likelihood of the next child being affected by CGD. Ninety-one families with at least one child affected by AR-CGD entered this study. Out of the 270 children, 128 were affected by AR-CGD. We used a cross tab for the odds ratio (OR) calculation, in which exposure to a previously affected child and the next child’s status were evaluated. This study illustrated that the chances of having another child afflicted with AR-CGD are significantly increased if the previous child had AR-CGD (OR=2.77, 95% CI=1.35-5.69). Although AR disorders affect 25% of each pregnancy, we showed that the chance that the next child would be affected by CGD, given that the previous child was affected, is 2.77 times greater than in families with a normal child. It is recommended to warn families with one or more affected children to evaluate the risk of CGD in their subsequent pregnancies with prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Complete TYK2 deficiency (IMMUNODEFICIENCY 35 OMIM (611521)) is a rare disorder, inherited as an autosomal recessive (AR) trait, which has been previously described in nine patients from seven unrelated kindreds [[1]-[3]]. Following mandatory BCG vaccination at birth in Iran and some other countries, patients with certain inborn errors of immunity may develop BCG disease that usually appears 3 months after the vaccination [[9]-[12]]. In line with other patients with complete AR TYK2 deficiency, our patient also suffers from viral disease, particularly with herpes viruses, attributable to an impaired IFN- -mediated immunity (2, 6). Importantly, both our patient and the patient reported in 2016 by Fuchs et al. carry the same TYK2 mutation and we thus infer that our patient would show a lack of TYK2 expression despite never tested. [Extracted from the article]

Chronic granulomatous disease (CGD) is a rare genetic disorder of neutrophil activity, resulting in increased rate of recurrent infections with catalase-positive bacteria and fungi, as well as various autoimmune diseases such as sarcoidosis, rheumatoid arthritis, and discoid and/or systemic lupus erythematosus. Few reports have reported lupus erythematosus (LE) in patients with X-linked CGD (XL-CGD) and carriers, and very few in autosomal recessive CGD (AR-CGD). Here, we present 5 patients with CGD developing LE at different ages to emphasize on the importance of appropriate follow-up and treatment in patients with CGD with clinical signs and symptoms of autoimmune diseases and even in those with negative serologic results. [ABSTRACT FROM AUTHOR]

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder due to a genetic defect in one of the components of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. This complex is composed of membrane-bound gp91-phox and p22-phox subunits, and cytosolic subunits consisting of p47-phox, p67-phox, and p40-phox. A mutation in CYBB gene encoding gp91-phox located on chromosome Xp21.1, leads to X-linked CGD. Herein, we report a 4-year-old Iranian boy presented with episodes of recurrent fever, cervical lymphadenopathy, and abdominal abscesses. Mutation analysis of the CYBB gene in the patient indicated a one-nucleotide deletion, c.316delT, resulting in p.W106GfsX. [ABSTRACT FROM AUTHOR]

Chronic granulomatous disease (CGD), a rare inherited primary immunodeficiency disorder, is caused by mutation in any one of the genes encoding components of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase enzyme. NCF2 gene (encoding P67-phox component) is one of them and its mutation is less common to cause CGD (around 5-6%). Here, we assessed mutation analysis of NCF2 in 4 CGD patients with p67-phox defect in Iran. These patients showed classical CGD symptoms. NCF2 sequence analyses revealed two different homozygous mutations including a nonsense mutation in exon 4, c.304C>T (Arg 102X) in one case and a CA deletion in exon 13 (Leu346fsX380) in one brother and sister; the latter is a new mutation which has not been reported in previous studies. In another patient in whom the attempts to amplify exon 2 individually from genomic DNA were unsuccessful, PCR amplification of exon 2 revealed no band of this exon on agarose gel. A PCR amplification mix of exon 2 and exon 7, with an internal control, confirmed the lack of exon 2 in this patient. Although a gross deletion in other exons of NCF2 has been previously reported, a large deletion encompassing exon 2 has been not reported yet. This abstract was also presented in ESID 2012, Florence, Italy. [ABSTRACT FROM AUTHOR]

Background: Chronic granulomatous disease (CGD) is a rare immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. We studied CGD inheritance forms (autosomal recessive (AR) or X-linked (XL)) and AR-CGD subtypes in Iran. Methods: Clinical and functional investigations were conducted in 93 Iranian CGD patients from 75 families. Results: Most of the patients were AR-CGD (87.1%). This was related to consanguineous marriages ( p = 0.001). The age of onset of symptoms and diagnosis were lower in XL-CGD compared with AR-CGD ( p < 0.0001 for both). Among AR-CGD patients, p47 phox defect was the predominant subtype (55.5%). The most common clinical features in patients were lymphadenopathy (65.6%) and pulmonary involvement (57%). XL-CGD patients were affected more frequently with severe infectious manifestations. Conclusions: Although XL-CGD is the most common type of the disease worldwide, only 12 patients (12.9%) were XL-CGD in our study. The relatively high frequency of AR-CGD is probable due to widely common consanguineous marriages in Iran. [ABSTRACT FROM AUTHOR]

One of the rarest forms of chronic granulomatous disease (CGD) is caused by mutations in CYBA, which encodes the p22-phox subunit of the phagocyte NADPH oxidase, leading to defective intracellular killing. This study investigated eight patients (six males and two females) from seven consanguineous, unrelated families with clinical CGD, positive family history and p22-phox deficiency. Mutation analysis of CYBA showed six different novel mutations: deletion of exons 3, 4 and 5; a missense mutation in exon 6 (c.373G>A); a splice site mutation in intron 5 (c.369+1G>A); a frameshift in exon 6 (c.385delGAGC); a frameshift in exon 3 (c.174delG); and a frameshift in exon 4 (c.223delC). [ABSTRACT FROM AUTHOR]

One of the components of NADPH oxidase is p47‐phox, encoded by NCF1 gene. This study aims to find new genetic changes and clinical features in 38 Iranian patients with autosomal recessive chronic granulomatous disease (AR‐CGD) caused by NCF1 gene defect. Patients who had abnormal NBT and DHR‐1,2,3 assay with loss of p47‐phox in Western blotting were included in this study. After recording demographic and clinical data, PCR amplification was performed followed by direct sequencing for all exons and exon‐intron boundaries. The most common form of CGD in Iran was AR‐CGD due to consanguinity marriages. Among patients with AR‐CGD, NCF1 deficiency was found to be more common than other forms. Cutaneous involvements (53%), pulmonary infections (50%) and lymphadenopathy (29%) were more prevalent than other clinical manifestations of CGD. Mutation analysis of NCF1 gene identified five different mutations. Homozygous delta GT deletion (c.75_76delGT) was the most frequent mutation and was detected in more than 63% of families. Six families had a nonsense mutation in exon 7 (c.579G > A). Two novel mutations were found in exon 4 in two families, including a missense mutation (c.328C > T) and a nine‐nucleotide deletion (c.331_339delTGTCCCCAC). Genetic detection of these mutations may result in early diagnosis and prevention of possible complications of the disease. This could be useful for timely decision‐making for haematopoietic stem cell transplantation and for carrier detection as well as prenatal diagnosis of next children in the affected families. Our findings might help to predict outcomes, raise awareness and help effective treatment in these patients. [ABSTRACT FROM AUTHOR]

Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency (approximately 1 case in 200.000-250.000 newborns) caused by defect in one of the components of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase enzyme (membrane-bound glycoproteins gp91, and cytosolic subunits p47-phox, p67-phox, p40-phox and p22-phox). This leads to defective intracellular killing by phagocyte cells. One of the components of NADPH-oxidase is p22-phox which is encoded by CYBA gene. In this study were identified new genetic changes of CYBA in 22 Iranian patients with autosomal recessive-CGD (AR-CGD). Methods: Twenty two CGD patients based on defect in NADPH oxidase activity (by NBT slide test and DHR-123 assay) and their demographic data and clinical histories were entered this study. They were referred to Immunology, Asthma and Allergy Research Institute (IAARI) for diagnosis and treatment. All patients had p22-phox deficiency based on western blotting. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) and PCR followed by direct sequencing to find p22-phox mutations. Results: Mutation analysis of CYBA revealed 12 different mutations, including three novel mutations: one deletion in exon 1, and two transitions in exon 3 [c.136G>A (p.Gly46Ser)], and exon 6 [c.388C>T (p.Gln130X)]. Conclusions: Three new mutations of CYBA gene in 4 of 22 Iranian patients with AR-CGD were found. These 3 novel mutations can partly complete the data base of Human Gene Mutation Database (HGMD). It can also be helpful for further prenatal diagnosis of next children in the affected families. Also it will be useful for timely decision making in bone marrow transplantation as treatment for CGD patients. [ABSTRACT FROM AUTHOR]