Familial candidiasis - CARD9, IL17RC, STAT1, CLEC7A, IL17F, IL17RA, RORC and TRAF3IP2 genes
Familial candidiasis or familial chronic mucocutaneous candidiasis is an inherited tendency to develop infections caused by Candida spp. Generally, affected individuals suffer from recurrent and persistent infections in the skin, nails and mucous membranes. This pattern of infection is called chronic mucocutaneous candidiasis.
Candida spp. it is generally present in the skin and mucous membranes, and most people do not cause health problems. However, certain drugs (such as antibiotics and corticosteroids) and other factors may contribute to occasional overgrowth of Candida spp. (candidiasis) in the oral or vaginal mucosa. Most people familiar with chronic or recurrent candidiasis suffer from chronic or recurrent yeast infections that begin in early childhood. These skin infections lead to a rash crusted and thickness patches; when these patches are produced on the scalp, can cause scarring alopecia in the affected area. Candidiasis of the nails can lead to thick nails, cracked and discolored and swelling and redness of the surrounding skin. Furthermore, individuals with familial candidiasis suffer frequent thrush and certain gastrointestinal symptoms such as bloating, constipation or diarrhea. Affected women may develop frequent vaginal infections, and children can have fungal infections on the skin that cause persistent diaper rash dermatitis.
Depending on the genetic change involved in this condition, some affected individuals are at risk of developing systemic candidiasis, a more serious condition in which the infection spreads through the bloodstream to various organs, including the brain and meninges. Systemic candidiasis can be potentially fatal.
Recurrent infections or chronic yeast can occur in people with no familial candidiasis. Some individuals suffer from recurrent candidiasis as part of a general susceptibility to infections because their immune system is affected by a disease such as acquired immune deficiency syndrome (AIDS) or severe combined immunodeficiency (SCID), medications, or other factors. Other individuals have syndromes such as APECED (autoimmune polyendocrinopathy -AP-, candidiasis and ectodermal dystrophy) or autosomal dominant hyper-IgE syndrome (AD-HIES) including a tendency to develop candidiasis along with other signs and symptoms affecting various organs and body systems.
There have identified mutations in several genes in people with familial candidiasis. Genes associated familial candidiasis encode proteins that are involved in immune system function. These genes include:
CARD9 gene (Caspase recruitment domain family, member 9), (9q34.3).
17RC gene (Interleukin 17 receptor C) (3p25.3).
STAT1 gene (Signal transducer and activator of transcription 1, 91kD) (2q32.2).
CLEC7A gene (C-type lectin domain family 7 member A), (12p13.2).
IL17F (interleukin 17F), (6p12).
17RA gene (Interleukin 17 receptor A), (22q11.1).
RORC gene (RAR related orphan receptor C) (1q21).
TRAF3IP2 gene (TRAF3 interacting protein 2), (6q21).
When the immune system recognizes Candida spp., it generates cells called Th17 cells. These cells produce cytokines known as interleukin-17 family (IL-17) as part of an immunological process known as IL-17 pathway. The route of IL-17 promotes inflammation, sending other cytokines and leukocytes that fight pathogens and promote tissue repair. Furthermore, the route of IL-17 promotes the production of certain segments of antimicrobial proteins (peptides) that control the growth of Candida spp. on the surface of mucous membranes.
Mutations of genes associated with familial candidiasis interfere with IL-17 pathway in several ways. Mutations in several genes, including the IL-17RC gene, deteriorate signaling pathway in IL-17. Mutations in other genes, including STAT1 and CARD9, are thought to block the pathway activity. The track deterioration IL-17 decreases the body´s immune response against Candida spp., which results in chronic or recurrent yeast infections that occur in people with familial candidiasis. Mutations in most genes described above, are associated with familial chronic mucocutaneous candidiasis; only CARD9 gene mutations have also been identified in some individuals with systemic candidiasis.
Familial candidiasis can be inherited with different patterns. People with this condition inherit a tendency to develop recurrent or chronic infections by Candida spp., but not their own infections. Familial candidiasis due to mutations in certain genes including STAT1, are inherited in an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the condition. Familial candidiasis due to mutations in other genes, such as CARD9 or IL17RC, is inherited as an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with familial candiadiasis, by means of the complete PCR amplification of the exons of the CARD9, IL17RC, STAT1, CLEC7A, IL17F, IL17RA, RORC and TRAF3IP2 genes, respectively, and their subsequent sequencing.
Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).