Materiały źródłowe

• #1 Chronic Granulomatous Disease: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1116022-overview

  Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defects in any of the five subunits of the NADPH oxidase complex responsible for the respiratory burst in phagocytic leukocytes. […] Chronic granulomatous disease (CGD) is a rare (1:250,000 births) disease caused by mutations in any one of the five components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. […] The main defect in chronic granulomatous disease (CGD) is a failure of neutrophils, monocytes, macrophages, and eosinophils to mount a respiratory burst and, therefore, to generate superoxide anions and other reactive oxygen species derived from superoxide, such as hydrogen peroxide. This renders the patients susceptible to severe, recurrent bacterial and fungal infections.

• #2 Chronic granulomatous disease: a review of the infectious and inflammatory complications | Clinical and Molecular Allergy | Full Text

  https://clinicalmolecularallergy.biomedcentral.com/articles/10.1186/1476-7961-9-10

  Chronic Granulomatous Disease is the most commonly encountered immunodeficiency involving the phagocyte, and is characterized by repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. […] The disease is the result of a disorder of the NADPH oxidase system, culminating in an inability of the phagocyte to generate superoxide, leading to the defective killing of pathogenic organisms. […] CGD is the most commonly encountered disorder of phagocytes, and is characterized be repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. […] The disease is a disorder of the NADPH oxidase system, culminating in an inability of the phagocyte to generate superoxide, leading to the defective killing of pathogenic organisms.

• #3 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  Chronic granulomatous diseases (CGD) are a group of recurrent life-threatening infections caused by a hereditary defect in forming reactive oxygen species. […] Defective phagocyte NADPH oxidase causes the disease, which ultimately results in phagocytes’ inability to destroy certain microbes, such as neutrophils, monocytes, and macrophages. […] CGD arises from mutations resulting in loss or functional inactivation of the NADPH oxidase complex subunits. Various genes are associated with the 5 components of NADPH oxidase, and mutations to the gp91phox, p22phox, p47phox, p67phox, or p40phox genes up the NADPH oxidase complex account for most of the CGD phenotypes. […] The NOX2 (gp91phox) gene is encoded by CYBB (cytochrome b (-245), beta subunit), which is located on chromosome X. Approximately 70 percent of the CGD patients have the CYBB variant, which accounts for the greater prevalence of CGD in males.

• #4 Orphanet: Chronic granulomatous disease

  https://www.orpha.net/en/disease/detail/379

  A rare primary immunodeficiency, mainly affecting phagocytes, which is characterized by an increased susceptibility to severe and recurrent bacterial and fungal infections, along with the development of granulomas. […] CGD is caused by mutations in any one of the 6 genes encoding the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits or a critical stabilizer. A mutation in the CYBB gene (Xp21.1) is seen in 65% of cases in North America and Western Europe. The other 35% of cases are due to mutations in the CYBA (16q24), NCF1 (7q11.23), NCF2 (1q25), NCF4 (22q13.1) and CYBC1 (17q25.3) genes. […] A deficiency in the NADPH oxidase enzyme complex leads to decreased production of reactive oxygen species (used by phagocytes to kill bacteria and fungi).

• #5 Chronic Granulomatous Disease | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/chronic-granulomatous-disease

  Chronic granulomatous disease (CGD) is a condition that prevents the immune system from fighting off certain infections. […] CGD is caused by variations in one of five genes CYBA, CYBB, NCF1, NCF2 and NCF4. Most commonly, CGD is inherited in an X-linked pattern, either because the male patient’s mother was a carrier of the variant in CYBB or the child spontaneously developed abnormalities in the X-chromosome in this region at the time of conception. […] CGD may also be inherited in an autosomal recessive matter, as is the case with variants in CYBA, NCF1, NCF2 and NCF4. In these cases, for a child to have symptoms of chronic granulomatous disease, there must be two variants of the gene. […] Each of the five genes that cause CGD encode a different part of the enzyme NADPH oxidase, which is essential to a properly functioning immune system. […] When any of the five genes are abnormal, the NADPH oxidase does not function correctly to allow the neutrophils to properly fight infections; leaving the body vulnerable to viruses, bacteria and inflammation.

• #6 Chronic granulomatous disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/chronic-granulomatous-disease/

  Chronic granulomatous disease is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. […] Mutations in the CYBA, CYBB, NCF1, NCF2, or NCF4 gene can cause chronic granulomatous disease. […] The proteins produced from the affected genes are parts (subunits) of an enzyme complex called NADPH oxidase, which plays an essential role in the immune system. […] Mutations in the CYBA, CYBB, NCF1, NCF2, and NCF4 genes result in the production of proteins with little or no function or the production of no protein at all. […] Without any one of its subunit proteins, NADPH oxidase cannot assemble or function properly. […] A lack of NADPH oxidase leaves affected individuals vulnerable to many types of infection and excessive inflammation. […] Some people with chronic granulomatous disease do not have an identified mutation in any of these genes. The cause of the condition in these individuals is unknown.

• #7 Orphanet: Chronic granulomatous disease

  https://www.orpha.net/en/disease/detail/379

  A rare primary immunodeficiency, mainly affecting phagocytes, which is characterized by an increased susceptibility to severe and recurrent bacterial and fungal infections, along with the development of granulomas. […] CGD is caused by mutations in any one of the 6 genes encoding the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits or a critical stabilizer. A mutation in the CYBB gene (Xp21.1) is seen in 65% of cases in North America and Western Europe. The other 35% of cases are due to mutations in the CYBA (16q24), NCF1 (7q11.23), NCF2 (1q25), NCF4 (22q13.1) and CYBC1 (17q25.3) genes. […] A deficiency in the NADPH oxidase enzyme complex leads to decreased production of reactive oxygen species (used by phagocytes to kill bacteria and fungi).

• #8 Pediatric Chronic Granulomatous Disease: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/956936-overview

  Chronic granulomatous disease (CGD), an inherited disorder of phagocytic cells, results from an inability of phagocytes to produce bactericidal superoxide anions (O2-). […] CGD is known to be caused by a defect in the nicotinamide adenine dinucleotide phosphate (NADPH), reduced form, oxidase enzyme complex of phagocytes. […] The cause of chronic granulomatous disease is an inherited defect in one of the six components of phagocyte NADPH oxidase enzyme complex. […] The most common molecular defect in chronic granulomatous disease is a mutation in the CYBB (cytochrome B, b subunit) gene, which is located on the X chromosome and that encodes for gp91phox (the b subunit of flavocytochrome b558). […] The second most common mutation occurs in the NCF1 gene on chromosome 7, which encodes for p47phox.

• #9 Disease: Chronic Granulomatous Disease

  https://crisprmedicinenews.com/disease/card/chronic-granulomatous-disease/

  Most cases of CGD are caused by mutations in five genes that each encode a subunit of the NADPH oxidase enzyme complex that plays a crucial role in immune function. […] CGD is caused by genetic mutations in the CYBA, CYBB, NCF1, NCF2, CYBC1, or NCF4 genes. […] A mutation in the CYBB gene (Xp21.1) is found in approximately 65% of cases in North America and Western Europe. […] Some cases of CGD have unknown genetic causes.

• #10 Chronic Granulomatous Disease (CGD): Commonly Associated Pathogens, Diagnosis and Treatment

  https://www.mdpi.com/2076-2607/11/9/2233

  Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in the phagocytic function of the innate immune system owing to mutations in genes encoding the five subunits of the nicotinamide adenine dinucleotide phosphatase (NADPH) oxidase enzyme complex. […] CGD is caused by the impaired phagocytic function of the innate immune system cells owing to mutations in genes encoding the five subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme complex (OEC). […] The functional NADPH OEC comprises five subunits: two are localized in the cell membrane during the resting phase, and three are localized in the cytoplasm. […] Mutations in either the membrane or cytosolic domain disrupt the respiratory burst in phagocytes. […] It was demonstrated for the first time that EROS (CYBC1/C17ORF62) regulates abundance of the gp91phox-p22phox heterodimer of the phagocyte NADPH OEC in human cells.

• #11 A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease | Nature Communications

  https://www.nature.com/articles/s41467-018-06964-x

  Mutations in genes encoding subunits of the phagocyte NADPH oxidase complex are recognized to cause chronic granulomatous disease (CGD), a severe primary immunodeficiency. […] Here we describe how deficiency of CYBC1, a previously uncharacterized protein in humans (C17orf62), leads to reduced expression of NADPH oxidases main subunit (gp91phox) and results in CGD. […] Through WGS of two brothers diagnosed with CGD, we identify a homozygous loss-of-function mutation, p.Tyr2Ter, in CYBC1 (previously C17orf62). […] Our results indicate that CYBC1 is essential for successful formation of the NADPH oxidase complex, likely by acting as a chaperone. […] In summary, by leveraging an extensive population database we elucidate the role of a previously uncharacterized gene in humans and identify a novel cause of CGD.

• #12 Chronic granulomatous disease | Causes, Symptoms & Treatment | Britannica

  https://www.britannica.com/science/chronic-granulomatous-disease

  chronic granulomatous disease, a group of rare inherited diseases characterized by the inability of certain white blood cells called phagocytes to destroy invading microorganisms. […] There are several genetic defects that cause chronic granulomatous disease, all of which impair the ability of phagocytes to make hydrogen peroxide. […] In about two-thirds of cases, the disorder is sex-linked a defect occurs in a recessive gene on the X chromosome. […] In the remaining one-third of cases, a gene on another chromosome is responsible for the disease, and two copies of the defective gene, one from each parent, must be inherited for the disease to arise (a type of inheritance called autosomal recessive).

• #13 Chronic granulomatous disease Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/chronic-granulomatous-disease

  Chronic granulomatous disease (CGD) is an inherited disorder in which certain immune system cells do not function properly. CGD is characterized by repeated and severe infections. […] In CGD, immune system cells called phagocytes are unable to kill some types of bacteria and fungi. This disorder leads to long-term (chronic) and repeated (recurrent) infections. About half of CGD cases are passed down through families as a sex-linked recessive trait. This means that boys are more likely to get the disorder than girls. The variant gene is carried on the X chromosome. A girl must inherit the variant X gene from each parent in order to have the disease.

• #14

  https://www.nicklauschildrens.org/conditions/chronic-granulomatous-disease

  Chronic granulomatous disease (CGD) is the disorder that develops when this cell doesnt function properly. […] CGD is an inherited disease, most frequently (two thirds of the time) the abnormal gene being carried by the mother (X-linked) and inherited by a son. […] In the other cases, inheritance is in autosomal recessive fashion (to have the disease a child must have two abnormal genes, inheriting one from each parent).

• #15 Chronic Granulomatous Disease: The European Experience | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0005234

  CGD is an immunodeficiency caused by deletions or mutations in genes that encode subunits of the leukocyte NADPH oxidase complex. […] CGD is caused by a defect in the burst of oxygen consumption that normally accompanies phagocytosis in myeloid cells (i.e. neutrophils, eosinophils, monocytes, and macrophages). […] The enzyme that catalyzes the respiratory burst, the leukocyte NADPH oxidase, consists of subunits, four of which are important for CGD (designated phox for phagocyte oxidase): gp91phox (or Nox2) and p22phox, located in membranes, as well as two cytosolic oxidase components, p47phox and p67phox. CGD is caused by a defect in any of these four components. […] Mutations in the gp91phox gene (CYBB on chromosome Xp21.1) cause the X-linked recessive form of the disease that affects the majority of CGD patients (70%).

• #16 Chronic granulomatous disease – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/chronic-granulomatous-disease/symptoms-causes/syc-20355817

  Chronic granulomatous (gran-u-LOM-uh-tus) disease (CGD) is a genetic condition in which infection-fighting white blood cells don’t work properly. […] CGD is inherited, meaning it runs in families. […] A change in one of five genes can cause CGD. People with CGD inherit the changed gene from a parent. These genes produce proteins that form an enzyme. This enzyme helps your immune system work properly. […] When there are changes to one of these genes, the protective proteins are not produced. Or they’re produced, but they don’t work properly. […] Some people with CGD don’t have one of these changed genes. In these cases, medical professionals don’t know what causes the condition.

• #17 Chronic granulomatous disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/chronic-granulomatous-disease/

  Chronic granulomatous disease is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. […] Mutations in the CYBA, CYBB, NCF1, NCF2, or NCF4 gene can cause chronic granulomatous disease. […] The proteins produced from the affected genes are parts (subunits) of an enzyme complex called NADPH oxidase, which plays an essential role in the immune system. […] Mutations in the CYBA, CYBB, NCF1, NCF2, and NCF4 genes result in the production of proteins with little or no function or the production of no protein at all. […] Without any one of its subunit proteins, NADPH oxidase cannot assemble or function properly. […] A lack of NADPH oxidase leaves affected individuals vulnerable to many types of infection and excessive inflammation. […] Some people with chronic granulomatous disease do not have an identified mutation in any of these genes. The cause of the condition in these individuals is unknown.

• #18 Chronic Granulomatous Disease: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1116022-overview

  Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defects in any of the five subunits of the NADPH oxidase complex responsible for the respiratory burst in phagocytic leukocytes. […] Chronic granulomatous disease (CGD) is a rare (1:250,000 births) disease caused by mutations in any one of the five components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. […] The main defect in chronic granulomatous disease (CGD) is a failure of neutrophils, monocytes, macrophages, and eosinophils to mount a respiratory burst and, therefore, to generate superoxide anions and other reactive oxygen species derived from superoxide, such as hydrogen peroxide. This renders the patients susceptible to severe, recurrent bacterial and fungal infections.

• #19 Chronic granulomatous disease: a review of the infectious and inflammatory complications | Clinical and Molecular Allergy | Full Text

  https://clinicalmolecularallergy.biomedcentral.com/articles/10.1186/1476-7961-9-10

  Chronic Granulomatous Disease is the most commonly encountered immunodeficiency involving the phagocyte, and is characterized by repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. […] The disease is the result of a disorder of the NADPH oxidase system, culminating in an inability of the phagocyte to generate superoxide, leading to the defective killing of pathogenic organisms. […] CGD is the most commonly encountered disorder of phagocytes, and is characterized be repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. […] The disease is a disorder of the NADPH oxidase system, culminating in an inability of the phagocyte to generate superoxide, leading to the defective killing of pathogenic organisms.

• #20 Chronic Granulomatous Disease (CGD): Commonly Associated Pathogens, Diagnosis and Treatment

  https://www.mdpi.com/2076-2607/11/9/2233

  Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in the phagocytic function of the innate immune system owing to mutations in genes encoding the five subunits of the nicotinamide adenine dinucleotide phosphatase (NADPH) oxidase enzyme complex. […] CGD is caused by the impaired phagocytic function of the innate immune system cells owing to mutations in genes encoding the five subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme complex (OEC). […] The functional NADPH OEC comprises five subunits: two are localized in the cell membrane during the resting phase, and three are localized in the cytoplasm. […] Mutations in either the membrane or cytosolic domain disrupt the respiratory burst in phagocytes. […] It was demonstrated for the first time that EROS (CYBC1/C17ORF62) regulates abundance of the gp91phox-p22phox heterodimer of the phagocyte NADPH OEC in human cells.

• #21 Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era

  https://www.mdpi.com/2077-0383/13/15/4435

  Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. […] Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. […] CGD can occur sporadically, but also demonstrates inheritance in X-linked recessive (XR) and autosomal recessive (AR) patterns. […] Deficiency of any one subunit of NADPH oxidase (gp91phox, p22phox, p47phox, p67phox, p40phox) or of other factors that contribute to the respiratory burst pathway may culminate in CGD or a CGD-like phagocyte disorder.

• #22 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  Chronic granulomatous diseases (CGD) are a group of recurrent life-threatening infections caused by a hereditary defect in forming reactive oxygen species. […] Defective phagocyte NADPH oxidase causes the disease, which ultimately results in phagocytes’ inability to destroy certain microbes, such as neutrophils, monocytes, and macrophages. […] CGD arises from mutations resulting in loss or functional inactivation of the NADPH oxidase complex subunits. Various genes are associated with the 5 components of NADPH oxidase, and mutations to the gp91phox, p22phox, p47phox, p67phox, or p40phox genes up the NADPH oxidase complex account for most of the CGD phenotypes. […] The NOX2 (gp91phox) gene is encoded by CYBB (cytochrome b (-245), beta subunit), which is located on chromosome X. Approximately 70 percent of the CGD patients have the CYBB variant, which accounts for the greater prevalence of CGD in males.

• #23 Causes of Chronic Granulomatous Disease (CGD)

  https://www.medindia.net/health/conditions/chronic-granulomatous-disease-causes.htm

  In Chronic granulomatous disease the white cells of the body or phagocytic cells are unable to kill certain bacteria and fungi. This situation arises due to a defect in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. NADPH oxidase is a membrane bound enzyme complex that takes part in the generation of superoxides or anti-oxidants. Superoxides kill bacteria and fungi. Phagocytes (cells that engulf and digest debris and invading microorganisms) from patients with CGD can migrate normally to sites of infection, ingest infecting microbes and even dump digestive enzymes and other antimicrobial substances into the phagosome. But they lack the enzymatic system required to produce oxidants which are required to kill microbes. […] Hence CGD patients are susceptible to infections with a special subset of bacteria and fungi, especially the ones that require hydrogen peroxide for control. […] CGD patients are immune to most viruses and to some kinds of bacteria and fungi; hence they are necessarily not infected all the time.

• #24 Chronic Granulomatous Disease (CGD) – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/chronic-granulomatous-disease-cgd

  Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder that involves phagocytic cell defects. More than 50% of cases of CGD are inherited as an X-linked recessive trait and thus occur only in males; in the rest, inheritance is autosomal recessive. Common mutations responsible for CGD affect the gp91phox(X-linked form),p22phox, p47phox, and p67phox genes. […] In CGD, white blood cells (WBCs) do not produce hydrogen peroxide, superoxide, and other activated oxygen compounds because nicotinamide adenine dinucleotide phosphate oxidase activity is deficient. Phagocytic cell microbicidal function is defective; thus, bacteria and fungi are not killed despite normal phagocytosis. […] Diagnosis of chronic granulomatous disease is by a flow cytometric oxidative (respiratory) burst assay to detect oxygen radical production using dihydrorhodamine 123 (DHR) or nitroblue tetrazolium (NBT). This test can also identify female carriers of the X-linked form and recessive forms. In these forms, the assay using DHR demonstrates 2 populations of phagocytes, normal and affected.

• #25 Pediatric Chronic Granulomatous Disease: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/956936-overview

  Mutations in the genes NCF2 (which encodes p67phox) and CYBA (which encodes p22phox) are rare, accounting for fewer than 10% of all cases of CGD. […] About 95% of the mutations mentioned above result in the complete absence or a greatly diminished level of the affected protein. […] Less than 10% of patients have the X-linked variant form of CGD (X91-), which has a relatively mild clinical course. […] The CGD phagocyte can kill numerous microorganisms despite its defects because most microorganisms endogenously produce hydrogen peroxide, which the CGD-affected phagocyte can modify and use against the organism in the phagosome.

• #26 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  In some cases, the mutations still render the NADPH oxidase partially intact, and consequentially, the disease phenotype is less severe. However, this depends largely on the gene mutated, the type of mutation, and the position of the mutation within the gene. […] CGD is due to a failure of the patients phagocytic leucocytes to kill various pathogens due to defective NADPH oxidase. This ultimately leads to poor ROS formation, a key molecule in the destruction of microbes. […] The prognosis of CGD is improving with advancements in treatment. Patients can prevent infection with good skin hygiene, antifungals, and antibiotics. Autosomal recessive forms of CGD have a better prognosis compared to X-linked CGD.

• #27 Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era

  https://www.mdpi.com/2077-0383/13/15/4435

  Mutation of this gene accounts for XR disease and 65–70% of all CGD. […] Most cases of CYBB-related CGD are hemizygous males, although haploinsufficient females with very skewed XCI are also well-recognised, and show predominantly autoimmune phenotypes. […] NCF1 (neutrophil cytosolic factor 1) encodes p47phox, and mutation of this gene accounts for about 20% of all CGD. […] Overall, neutrophils deficient in the respiratory burst show defective killing of microorganisms by phagocytosis, neutrophil extracellular traps, and other forms of regulated cell death. […] The heterogeneity of clinical phenotypes observed in CGD is reflected in the variety of mutations identified in responsible genes. […] Confirmation of a CGD diagnosis following positive functional testing is established by identifying a pathogenic variant in one of the CGD-related genes that encode or permit assembly or function of NADPH oxidase.

• #28 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Chronic-Granulomatous-Disease.aspx

  Chronic granulomatous disease (CGD) is a rare genetic immunodeficiency associated with phagocyte function. It is caused due to functional impairment in the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase complex and affects 1 in 200,000 live births in the USA. […] CGD occurs due to NADPH oxidase complex dysfunction in neutrophilic granulocytes and monocytes. It is due to mutations that inactivate NOX2 and its auxiliary proteins. […] The most common form of CGD is the X-linked form, caused by mutations in the CYBB gene – found on the X chromosome and codes for NOX2. […] CYBB mutations range from single nucleotide changes to megabase deletions. Missense, nonsense mutations (direct or by frameshift) produce a stop codon farther downstream, causing protein synthesis to be terminated prematurely.

• #29 A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease | Nature Communications

  https://www.nature.com/articles/s41467-018-06964-x

  Mutations in genes encoding subunits of the phagocyte NADPH oxidase complex are recognized to cause chronic granulomatous disease (CGD), a severe primary immunodeficiency. […] Here we describe how deficiency of CYBC1, a previously uncharacterized protein in humans (C17orf62), leads to reduced expression of NADPH oxidases main subunit (gp91phox) and results in CGD. […] Through WGS of two brothers diagnosed with CGD, we identify a homozygous loss-of-function mutation, p.Tyr2Ter, in CYBC1 (previously C17orf62). […] Our results indicate that CYBC1 is essential for successful formation of the NADPH oxidase complex, likely by acting as a chaperone. […] In summary, by leveraging an extensive population database we elucidate the role of a previously uncharacterized gene in humans and identify a novel cause of CGD.

• #30 A novel mutation in EROS (CYBC1) causes Chronic Granulomatous Disease | medRxiv

  https://www.medrxiv.org/content/10.1101/2023.04.21.23286144v1

  Chronic Granulomatous Disease (CGD) is an inborn error of immunity characterised by opportunistic infection and sterile granulomatous inflammation. CGD is caused by a failure of reactive oxygen species (ROS) production by the phagocyte NADPH oxidase. Mutations in the genes encoding phagocyte NADPH oxidase subunits cause CGD. […] We describe a homozygous frameshift mutation in CYBC1 leading to CGD. Individuals who are heterozygous for this mutation are found in South Asian populations (allele frequency = 0.00006545), thus it is not a private mutation. Therefore, it is likely to be the underlying cause of other cases of CGD.

• #31 Pediatric Chronic Granulomatous Disease: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/956936-overview

  Chronic granulomatous disease (CGD), an inherited disorder of phagocytic cells, results from an inability of phagocytes to produce bactericidal superoxide anions (O2-). […] CGD is known to be caused by a defect in the nicotinamide adenine dinucleotide phosphate (NADPH), reduced form, oxidase enzyme complex of phagocytes. […] The cause of chronic granulomatous disease is an inherited defect in one of the six components of phagocyte NADPH oxidase enzyme complex. […] The most common molecular defect in chronic granulomatous disease is a mutation in the CYBB (cytochrome B, b subunit) gene, which is located on the X chromosome and that encodes for gp91phox (the b subunit of flavocytochrome b558). […] The second most common mutation occurs in the NCF1 gene on chromosome 7, which encodes for p47phox.

• #32 Chronic Granulomatous Disease: A Comprehensive Guide

  https://www.rupahealth.com/post/chronic-granulomatous-disease-a-comprehensive-guide

  Chronic granulomatous disease (CGD) is a rare genetic disorder that affects the immune system, making it difficult for the body to fight off bacterial and fungal infections. […] It is caused by gene mutations responsible for NADPH oxidase, an enzyme complex in white blood cells. […] CGD results from mutations in genes that control NADPH oxidase, the enzyme complex needed for white blood cells to destroy bacteria and fungi. […] The key genes affected include: CYBB (gp91phox): Located on the X chromosome, responsible for the most common X-linked form of CGD. […] NCF1 (p47phox), CYBA (p22phox), NCF2 (p67phox), and NCF4 (p40phox): are associated with autosomal recessive CGD. […] The severity of CGD depends on the mutation type: Some mutations allow partial enzyme activity, leading to milder symptoms. […] Others cause complete enzyme loss, resulting in severe, early-onset infections.

• #33 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  In some cases, the mutations still render the NADPH oxidase partially intact, and consequentially, the disease phenotype is less severe. However, this depends largely on the gene mutated, the type of mutation, and the position of the mutation within the gene. […] CGD is due to a failure of the patients phagocytic leucocytes to kill various pathogens due to defective NADPH oxidase. This ultimately leads to poor ROS formation, a key molecule in the destruction of microbes. […] The prognosis of CGD is improving with advancements in treatment. Patients can prevent infection with good skin hygiene, antifungals, and antibiotics. Autosomal recessive forms of CGD have a better prognosis compared to X-linked CGD.

• #34

  https://link.springer.com/article/10.1007/s10875-023-01541-4

  Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency disorder of phagocytes, characterized by recurrent fungal and bacterial infections. […] CGD is characterized by recurrent fungal and bacterial infections and hyper-inflammatory and autoimmune symptoms. […] A CYBC1 gene mutation leads to reduced expression of NADPH oxidase main subunit (gp91phox) and may result in CGD. […] The significant prevalence of AR forms of CGD (76.3%) is related to the high rate of consanguinity (81.5%), consistent with data from Egypt, Israel, Iran, and Turkey that were previously published. […] The p47phox group had significantly higher SI as well as overall survival rate, and these findings were reported in several previous studies. […] It is important to mention that we diagnosed three male patients with gp91phox/ p22phox deficiency, and their mothers were not available to be tested for carrier pattern with the possibility of being CYBC1 deficient patients.

• #35 Pediatric Chronic Granulomatous Disease: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/956936-overview

  Mutations in the genes NCF2 (which encodes p67phox) and CYBA (which encodes p22phox) are rare, accounting for fewer than 10% of all cases of CGD. […] About 95% of the mutations mentioned above result in the complete absence or a greatly diminished level of the affected protein. […] Less than 10% of patients have the X-linked variant form of CGD (X91-), which has a relatively mild clinical course. […] The CGD phagocyte can kill numerous microorganisms despite its defects because most microorganisms endogenously produce hydrogen peroxide, which the CGD-affected phagocyte can modify and use against the organism in the phagosome.

• #36 SciELO Brazil – Chronic granulomatous disease: why an inflammatory disease? Chronic granulomatous disease: why an inflammatory disease?

  https://www.scielo.br/j/bjmbr/a/GFn4cFkyc8VvDggkfD3nW4S/?lang=en

  The main manifestations are represented prominently by granulomas, as well as colitis, which is frequent and leads to substantial morbidity. […] Defects of microbicidal activity can facilitate the persistence of pathogens and increase the inflammatory response in some patients. […] Granulomas can occur in most instances without an infectious pathogen. […] The primary mechanism of the increased inflammatory response remains poorly understood. […] A deficiency in the NADPH oxidase system in CGD patient phagocytes leads to reduced degradation of phagocytosed material or apoptotic cells, which implicates either the remaining phagocytosed pathogen or apoptotic neutrophils phagocytosed by macrophages, such as pathognomonic eosinophilic crystals. […] The trend to develop granulomatous complications in CGD patients appears to be influenced by genetic modifiers.

• #37 Chronic Granulomatous Disease (CGD): Commonly Associated Pathogens, Diagnosis and Treatment

  https://www.mdpi.com/2076-2607/11/9/2233

  Essential reactive oxygen species (EROS) mutations are a novel cause of chronic granulomatous disease. […] Molecular defects in any of these five genes (CYBB for gp91phox (located on the X chromosome), CYBA for p22phox, NCF1 for p47phox, NCF2 for p67phox, and NCF4 for p40phox) can occur in 90% of patients with CGD. […] Symptoms may be delayed in some patients with residual activity. […] In most countries, the offspring of CGD consanguineous marriages or unions is at increased risk of CGD due to expressing autosomal recessive gene mutations inherited from common CGD ancestors. […] Therefore, consanguineous unions increase the incidence of this condition, which sometimes is not detected quickly enough, and death from infectious diseases may occur.

• #38 Study finds CGD carriers exhibit symptoms of disorder | Immune Deficiency Foundation

  https://primaryimmune.org/resources/news-articles/study-finds-cgd-carriers-exhibit-symptoms-disorder

  Prior research studies have shown that female X-linked carriers of chronic granulomatous disease (CGD) mothers, daughters, sisters, aunts, and grandmothers exhibit some symptoms related to the disease. […] CGD, a rare primary immunodeficiency (PI), occurs when a persons white blood cells do not produce enough superoxide. […] Changes in any one of six genes cause CGD, with 66 percent of cases being X-linked and the remainder, autosomal recessive. […] Over the last several years, several studies have shown that in addition to passing on the CGD gene to their children, X-linked carriers can suffer symptoms themselves. […] Leiding said this study bears out that X-linked female CGD carriers can have CGD-related infections, and many require the use of anti-microbial prophylaxis. […] The major points I want to make when we eventually publish this manuscript is, again, that this is its own entity and that many of our patients need to be followed by specialty care, said Leiding, adding that X-linked CGD carriers should seek treatment from specialists such as immunologists, hematologists/oncologists, and rheumatologists. […] Some of those health problems include: Increased risk of infection. […] However, recent studies show that carriers have autoimmune and inflammatory manifestations and that its important for women to undergo testing to determine how much they may be affected.

• #39

  https://link.springer.com/article/10.1007/s10875-023-01541-4

  Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency disorder of phagocytes, characterized by recurrent fungal and bacterial infections. […] CGD is characterized by recurrent fungal and bacterial infections and hyper-inflammatory and autoimmune symptoms. […] A CYBC1 gene mutation leads to reduced expression of NADPH oxidase main subunit (gp91phox) and may result in CGD. […] The significant prevalence of AR forms of CGD (76.3%) is related to the high rate of consanguinity (81.5%), consistent with data from Egypt, Israel, Iran, and Turkey that were previously published. […] The p47phox group had significantly higher SI as well as overall survival rate, and these findings were reported in several previous studies. […] It is important to mention that we diagnosed three male patients with gp91phox/ p22phox deficiency, and their mothers were not available to be tested for carrier pattern with the possibility of being CYBC1 deficient patients.

• #40 Symptoms and Sequelae of Chronic Granulomatous Disease – For HCPs

  https://www.cgdpathways.com/cgd-overview/symptoms-and-sequelae-of-chronic-granulomatous-disease

  Osteomyelitis, hepatic abscess, and lymphadenitis may be signs of chronic granulomatous disease.1 […] Infections and granulomatous lesions are usually the first manifestations of CGD, with the skin being among the most frequently impacted sites.1 […] Gastrointestinal symptoms indicative of CGD may include pyloric edema, abdominal pain, diarrhea, and perirectal granulomas.1 […] Many severe infections in patients with CGD in North America are caused by a select group of organisms, both bacterial and fungal.1,5-10 Most of these pathogens, including Aspergillus, Nocardia, Serratia, Burkholderia, Klebsiella, and Staphylococcus aureus, are catalase-positive.5,6 In patients with CGD, these catalase-positive pathogens are noteworthy because they can neutralize some of the hydrogen peroxide produced by neutrophils other than those in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.6 […] Staphylococcus aureus, Burkholderia cepacia complex, Serratia marcescens, and Nocardia species are the primary causes of most infections in individuals with CGD.1,9

• #41 Causes of Chronic Granulomatous Disease (CGD)

  https://www.medindia.net/health/conditions/chronic-granulomatous-disease-causes.htm

  In Chronic granulomatous disease the white cells of the body or phagocytic cells are unable to kill certain bacteria and fungi. This situation arises due to a defect in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. NADPH oxidase is a membrane bound enzyme complex that takes part in the generation of superoxides or anti-oxidants. Superoxides kill bacteria and fungi. Phagocytes (cells that engulf and digest debris and invading microorganisms) from patients with CGD can migrate normally to sites of infection, ingest infecting microbes and even dump digestive enzymes and other antimicrobial substances into the phagosome. But they lack the enzymatic system required to produce oxidants which are required to kill microbes. […] Hence CGD patients are susceptible to infections with a special subset of bacteria and fungi, especially the ones that require hydrogen peroxide for control. […] CGD patients are immune to most viruses and to some kinds of bacteria and fungi; hence they are necessarily not infected all the time.

• #42 Symptoms and Sequelae of Chronic Granulomatous Disease – For HCPs

  https://www.cgdpathways.com/cgd-overview/symptoms-and-sequelae-of-chronic-granulomatous-disease

  Osteomyelitis, hepatic abscess, and lymphadenitis may be signs of chronic granulomatous disease.1 […] Infections and granulomatous lesions are usually the first manifestations of CGD, with the skin being among the most frequently impacted sites.1 […] Gastrointestinal symptoms indicative of CGD may include pyloric edema, abdominal pain, diarrhea, and perirectal granulomas.1 […] Many severe infections in patients with CGD in North America are caused by a select group of organisms, both bacterial and fungal.1,5-10 Most of these pathogens, including Aspergillus, Nocardia, Serratia, Burkholderia, Klebsiella, and Staphylococcus aureus, are catalase-positive.5,6 In patients with CGD, these catalase-positive pathogens are noteworthy because they can neutralize some of the hydrogen peroxide produced by neutrophils other than those in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.6 […] Staphylococcus aureus, Burkholderia cepacia complex, Serratia marcescens, and Nocardia species are the primary causes of most infections in individuals with CGD.1,9

• #43 Chronic Granulomatous Disease: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1116022-overview

  Most infections in CGD are caused by Staphylococcus aureus. Infections are also caused by unusual opportunistic organisms such as Chromobacterium violaceum; Serratia marcescens; and Nocardia, Legionella, and atypical Mycobacteria species. […] BCG vaccination may cause CGD. […] Fungal infections in CGD patients have been reported to account for approximately 20% of infections. The most common fungal infections in these patients are caused by Aspergillus species. The spectrum of infection caused by Aspergillus species varies from flulike pneumonia to life-threatening invasive aspergillosis. The most common form of aspergillosis in chronic granulomatous disease patients is Aspergillus pneumonia, which can be accompanied by dissemination to the ribs, chest wall, and soft tissues. Infections with Aspergillus species, particularly of the lungs or bones, are difficult to eradicate.

• #44 SciELO Brazil – Chronic granulomatous disease: why an inflammatory disease? Chronic granulomatous disease: why an inflammatory disease?

  https://www.scielo.br/j/bjmbr/a/GFn4cFkyc8VvDggkfD3nW4S/?lang=en

  Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the genes encoding subunits of the phagocytic NADPH oxidase system. […] Chronic granulomatous disease (CGD) is a fatal primary immunodeficiency caused by mutations in the genes encoding subunits of the NADPH oxidase system, which consists of five subunits. […] These defects lead to a failure of phagocytes to catalytically convert oxygen to superoxide and other reactive oxygen species (ROS) that play a key role in killing intracellular pathogens. […] The main causes of infections in CGD patients are Staphylococcus aureus, Burkholderia cepacia, Pseudomonas, Serratia marcescens, Aspergillus, and Nocardia species. […] NADPH oxidase deficiency has been seen predominantly as an immunodeficiency, characterized by an inability to mount an inflammatory response. However, there is current evidence for hyperinflammatory complications of CGD.

• #45

  https://link.springer.com/article/10.1007/s10875-023-01541-4

  The most common isolated organism from pulmonary infections was Aspergillus sp., followed by gram-negative bacteria then Mycobacterial sp., like in many reports. […] The most common site of mycobacterial infection was the lymph nodes 17/44 (38.6%), followed by the lungs 13/44 (29.5%). […] The most common cause of mortality, similar to the European and Indian reports, was pneumonia.

• #46 Causes of Chronic Granulomatous Disease (CGD)

  https://www.medindia.net/health/conditions/chronic-granulomatous-disease-causes.htm

  In Chronic granulomatous disease the white cells of the body or phagocytic cells are unable to kill certain bacteria and fungi. This situation arises due to a defect in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. NADPH oxidase is a membrane bound enzyme complex that takes part in the generation of superoxides or anti-oxidants. Superoxides kill bacteria and fungi. Phagocytes (cells that engulf and digest debris and invading microorganisms) from patients with CGD can migrate normally to sites of infection, ingest infecting microbes and even dump digestive enzymes and other antimicrobial substances into the phagosome. But they lack the enzymatic system required to produce oxidants which are required to kill microbes. […] Hence CGD patients are susceptible to infections with a special subset of bacteria and fungi, especially the ones that require hydrogen peroxide for control. […] CGD patients are immune to most viruses and to some kinds of bacteria and fungi; hence they are necessarily not infected all the time.

• #47 Pediatric Chronic Granulomatous Disease: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/956936-overview

  Mutations in the genes NCF2 (which encodes p67phox) and CYBA (which encodes p22phox) are rare, accounting for fewer than 10% of all cases of CGD. […] About 95% of the mutations mentioned above result in the complete absence or a greatly diminished level of the affected protein. […] Less than 10% of patients have the X-linked variant form of CGD (X91-), which has a relatively mild clinical course. […] The CGD phagocyte can kill numerous microorganisms despite its defects because most microorganisms endogenously produce hydrogen peroxide, which the CGD-affected phagocyte can modify and use against the organism in the phagosome.

• #48 SciELO Brazil – Chronic granulomatous disease: why an inflammatory disease? Chronic granulomatous disease: why an inflammatory disease?

  https://www.scielo.br/j/bjmbr/a/GFn4cFkyc8VvDggkfD3nW4S/?lang=en

  Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the genes encoding subunits of the phagocytic NADPH oxidase system. […] Chronic granulomatous disease (CGD) is a fatal primary immunodeficiency caused by mutations in the genes encoding subunits of the NADPH oxidase system, which consists of five subunits. […] These defects lead to a failure of phagocytes to catalytically convert oxygen to superoxide and other reactive oxygen species (ROS) that play a key role in killing intracellular pathogens. […] The main causes of infections in CGD patients are Staphylococcus aureus, Burkholderia cepacia, Pseudomonas, Serratia marcescens, Aspergillus, and Nocardia species. […] NADPH oxidase deficiency has been seen predominantly as an immunodeficiency, characterized by an inability to mount an inflammatory response. However, there is current evidence for hyperinflammatory complications of CGD.

• #49 Chronic Granulomatous Disease (CGD) > Clinical Keywords > Yale Medicine

  https://www.yalemedicine.org/clinical-keywords/chronic-granulomatous-disease

  Chronic granulomatous disease (CGD) is a rare genetic disorder characterized by a malfunctioning immune system, leading to recurrent and severe bacterial and fungal infections. […] The condition results from mutations in genes responsible for producing proteins that help white blood cells kill pathogens. […] This defect causes the formation of granulomas, which are clusters of immune cells that form at sites of infection or inflammation.

• #50 SciELO Brazil – Chronic granulomatous disease: why an inflammatory disease? Chronic granulomatous disease: why an inflammatory disease?

  https://www.scielo.br/j/bjmbr/a/GFn4cFkyc8VvDggkfD3nW4S/?lang=en

  The main manifestations are represented prominently by granulomas, as well as colitis, which is frequent and leads to substantial morbidity. […] Defects of microbicidal activity can facilitate the persistence of pathogens and increase the inflammatory response in some patients. […] Granulomas can occur in most instances without an infectious pathogen. […] The primary mechanism of the increased inflammatory response remains poorly understood. […] A deficiency in the NADPH oxidase system in CGD patient phagocytes leads to reduced degradation of phagocytosed material or apoptotic cells, which implicates either the remaining phagocytosed pathogen or apoptotic neutrophils phagocytosed by macrophages, such as pathognomonic eosinophilic crystals. […] The trend to develop granulomatous complications in CGD patients appears to be influenced by genetic modifiers.

• #51 Frontiers | Chronic Granulomatous Disease First Diagnosed in Adulthood Presenting With Spinal Cord Infection

  https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01258/full

  Genetic examination confirmed the diagnosis CGD as a total lack of the NCF1 sequence was found indicating a homozygous deletion, which has been described in only 24 families with CGD. […] Chronic granulomatous disease manifests with repeated severe bacterial and fungal infections resulting in the formation of granulomas.

• #52 SciELO Brazil – Chronic granulomatous disease: why an inflammatory disease? Chronic granulomatous disease: why an inflammatory disease?

  https://www.scielo.br/j/bjmbr/a/GFn4cFkyc8VvDggkfD3nW4S/?lang=en

  The main manifestations are represented prominently by granulomas, as well as colitis, which is frequent and leads to substantial morbidity. […] Defects of microbicidal activity can facilitate the persistence of pathogens and increase the inflammatory response in some patients. […] Granulomas can occur in most instances without an infectious pathogen. […] The primary mechanism of the increased inflammatory response remains poorly understood. […] A deficiency in the NADPH oxidase system in CGD patient phagocytes leads to reduced degradation of phagocytosed material or apoptotic cells, which implicates either the remaining phagocytosed pathogen or apoptotic neutrophils phagocytosed by macrophages, such as pathognomonic eosinophilic crystals. […] The trend to develop granulomatous complications in CGD patients appears to be influenced by genetic modifiers.

• #53 Chronic granulomatous disease – wikidoc

  https://www.wikidoc.org/index.php/Chronic_granulomatous_disease

  A low level of NADPH, the cofactor required for superoxide synthesis, can lead to CGD. This has been reported in women who are homozygous for the genetic defect causing glucose-6-phosphate dehydrogenase deficiency (G6PD), which is characterised by reduced NADPH levels. […] Gene therapy is currently being studied as a possible treatment for chronic granulomatous disease. CGD is well-suited for gene therapy since it is caused by a mutation in single gene which only affects one body system (the hematopoietic system).

• #54 Chronic Granulomatous Disease: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1116022-overview

  Most infections in CGD are caused by Staphylococcus aureus. Infections are also caused by unusual opportunistic organisms such as Chromobacterium violaceum; Serratia marcescens; and Nocardia, Legionella, and atypical Mycobacteria species. […] BCG vaccination may cause CGD. […] Fungal infections in CGD patients have been reported to account for approximately 20% of infections. The most common fungal infections in these patients are caused by Aspergillus species. The spectrum of infection caused by Aspergillus species varies from flulike pneumonia to life-threatening invasive aspergillosis. The most common form of aspergillosis in chronic granulomatous disease patients is Aspergillus pneumonia, which can be accompanied by dissemination to the ribs, chest wall, and soft tissues. Infections with Aspergillus species, particularly of the lungs or bones, are difficult to eradicate.

• #55 Chronic granulomatous disease – wikidoc

  https://www.wikidoc.org/index.php/Chronic_granulomatous_disease

  Chronic granulomatous disease (CGD) is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds (most importantly, the superoxide radical) used to kill certain ingested pathogens. This leads to the formation of granulomata in many organs. […] The underlying cellular mechanism that causes chronic granulomatous disease was discovered in 1967, and research since that time has further elucidated the molecular mechanisms underlying the disease. […] Most cases of chronic granulomatous disease are transmitted as a mutation on the X chromosome and are thus called an „X-linked trait”. The affected gene on the X chromosome codes for the gp91 protein p91-PHOX. CGD can also be transmitted in an autosomal recessive fashion and affects other PHOX proteins. The type of mutation that causes both types of CGD are varied and may be deletions, frame-shift, nonsense, and missense.

• #56 Chronic granulomatous disease: a review of the infectious and inflammatory complications | Clinical and Molecular Allergy | Full Text

  https://clinicalmolecularallergy.biomedcentral.com/articles/10.1186/1476-7961-9-10

  Chronic Granulomatous Disease is the most commonly encountered immunodeficiency involving the phagocyte, and is characterized by repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. […] The disease is the result of a disorder of the NADPH oxidase system, culminating in an inability of the phagocyte to generate superoxide, leading to the defective killing of pathogenic organisms. […] CGD is the most commonly encountered disorder of phagocytes, and is characterized be repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. […] The disease is a disorder of the NADPH oxidase system, culminating in an inability of the phagocyte to generate superoxide, leading to the defective killing of pathogenic organisms.

• #57 Orphanet: Chronic granulomatous disease

  https://www.orpha.net/en/disease/detail/379

  A rare primary immunodeficiency, mainly affecting phagocytes, which is characterized by an increased susceptibility to severe and recurrent bacterial and fungal infections, along with the development of granulomas. […] CGD is caused by mutations in any one of the 6 genes encoding the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits or a critical stabilizer. A mutation in the CYBB gene (Xp21.1) is seen in 65% of cases in North America and Western Europe. The other 35% of cases are due to mutations in the CYBA (16q24), NCF1 (7q11.23), NCF2 (1q25), NCF4 (22q13.1) and CYBC1 (17q25.3) genes. […] A deficiency in the NADPH oxidase enzyme complex leads to decreased production of reactive oxygen species (used by phagocytes to kill bacteria and fungi).

• #58 Disease: Chronic Granulomatous Disease

  https://crisprmedicinenews.com/disease/card/chronic-granulomatous-disease/

  Most cases of CGD are caused by mutations in five genes that each encode a subunit of the NADPH oxidase enzyme complex that plays a crucial role in immune function. […] CGD is caused by genetic mutations in the CYBA, CYBB, NCF1, NCF2, CYBC1, or NCF4 genes. […] A mutation in the CYBB gene (Xp21.1) is found in approximately 65% of cases in North America and Western Europe. […] Some cases of CGD have unknown genetic causes.

• #59 Chronic Granulomatous Disease: The European Experience | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0005234

  CGD is an immunodeficiency caused by deletions or mutations in genes that encode subunits of the leukocyte NADPH oxidase complex. […] CGD is caused by a defect in the burst of oxygen consumption that normally accompanies phagocytosis in myeloid cells (i.e. neutrophils, eosinophils, monocytes, and macrophages). […] The enzyme that catalyzes the respiratory burst, the leukocyte NADPH oxidase, consists of subunits, four of which are important for CGD (designated phox for phagocyte oxidase): gp91phox (or Nox2) and p22phox, located in membranes, as well as two cytosolic oxidase components, p47phox and p67phox. CGD is caused by a defect in any of these four components. […] Mutations in the gp91phox gene (CYBB on chromosome Xp21.1) cause the X-linked recessive form of the disease that affects the majority of CGD patients (70%).

• #60 Symptoms and Sequelae of Chronic Granulomatous Disease – For HCPs

  https://www.cgdpathways.com/cgd-overview/symptoms-and-sequelae-of-chronic-granulomatous-disease

  Osteomyelitis, hepatic abscess, and lymphadenitis may be signs of chronic granulomatous disease.1 […] Infections and granulomatous lesions are usually the first manifestations of CGD, with the skin being among the most frequently impacted sites.1 […] Gastrointestinal symptoms indicative of CGD may include pyloric edema, abdominal pain, diarrhea, and perirectal granulomas.1 […] Many severe infections in patients with CGD in North America are caused by a select group of organisms, both bacterial and fungal.1,5-10 Most of these pathogens, including Aspergillus, Nocardia, Serratia, Burkholderia, Klebsiella, and Staphylococcus aureus, are catalase-positive.5,6 In patients with CGD, these catalase-positive pathogens are noteworthy because they can neutralize some of the hydrogen peroxide produced by neutrophils other than those in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.6 […] Staphylococcus aureus, Burkholderia cepacia complex, Serratia marcescens, and Nocardia species are the primary causes of most infections in individuals with CGD.1,9

• #61 Frontiers | Chronic Granulomatous Disease First Diagnosed in Adulthood Presenting With Spinal Cord Infection

  https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01258/full

  Genetic examination confirmed the diagnosis CGD as a total lack of the NCF1 sequence was found indicating a homozygous deletion, which has been described in only 24 families with CGD. […] Chronic granulomatous disease manifests with repeated severe bacterial and fungal infections resulting in the formation of granulomas.

• #62 Chronic Granulomatous Disease: A Comprehensive Guide

  https://www.rupahealth.com/post/chronic-granulomatous-disease-a-comprehensive-guide

  Chronic granulomatous disease (CGD) is a rare genetic disorder that affects the immune system, making it difficult for the body to fight off bacterial and fungal infections. […] It is caused by gene mutations responsible for NADPH oxidase, an enzyme complex in white blood cells. […] CGD results from mutations in genes that control NADPH oxidase, the enzyme complex needed for white blood cells to destroy bacteria and fungi. […] The key genes affected include: CYBB (gp91phox): Located on the X chromosome, responsible for the most common X-linked form of CGD. […] NCF1 (p47phox), CYBA (p22phox), NCF2 (p67phox), and NCF4 (p40phox): are associated with autosomal recessive CGD. […] The severity of CGD depends on the mutation type: Some mutations allow partial enzyme activity, leading to milder symptoms. […] Others cause complete enzyme loss, resulting in severe, early-onset infections.

• #63 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  In some cases, the mutations still render the NADPH oxidase partially intact, and consequentially, the disease phenotype is less severe. However, this depends largely on the gene mutated, the type of mutation, and the position of the mutation within the gene. […] CGD is due to a failure of the patients phagocytic leucocytes to kill various pathogens due to defective NADPH oxidase. This ultimately leads to poor ROS formation, a key molecule in the destruction of microbes. […] The prognosis of CGD is improving with advancements in treatment. Patients can prevent infection with good skin hygiene, antifungals, and antibiotics. Autosomal recessive forms of CGD have a better prognosis compared to X-linked CGD.

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