Materiały źródłowe

• #1 Familial Mediterranean Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560754/

  Familial Mediterranean fever (FMF) is an autoinflammatory genetic disorder that mainly affects people of Mediterranean origin. […] FMF is characterized by recurrent episodes of fever and serositis (chest, abdomen, joints), leading to painful attacks early during childhood. […] FMF is an autosomal recessive disease. The gene responsible for FMF is the MEFV gene, which is located on the short arm of chromosome 16 (16 p13.3). […] Around 300 different mutations of the MEFV gene have been identified, which could lead to FMF. […] Mutations commonly occur in exons 2, 3, 5, and 10. […] Out of these mutations, V726A, M680I, E148Q, M694V, AND M694I mutations are responsible for around 70 to 80 percent of cases. […] About 10 percent of patients who are diagnosed clinically with FMF have no mutations in the MEFV gene.

• #1 Familial Mediterranean Fever: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/330284-overview

  FMF is a recessive genetic disease associated with missense and nonsense mutations in the MEFV gene, which is located on the short arm of chromosome 16. This gene codes for the protein known as pyrin or marenostrin. […] More than 310 sequence variants in the MEFV gene have been identified, although not all not associated with a disease phenotype. […] Most of the pathogenic mutations are in exon 10 of the gene between amino acids 680 and 761. […] Homozygotes for M694V (valine for methionine at position 694) may experience more severe disease and may be more likely to develop amyloidosis. […] Other genes may be involved in FMF. This possibility is supported by patients who meet criteria for FMF without identifiable mutations in MEFV and who have clinical manifestations that are indistinguishable from patients with MEFV mutations.

• #1 Familial Mediterranean Fever (FMF): What It Is & Symptoms

  https://my.clevelandclinic.org/health/diseases/familial-mediterranean-fever

  Familial Mediterranean fever (FMF) is a lifelong condition that causes recurring episodes of fever and inflammation throughout your body. Its a genetic disorder that mainly affects people of Mediterranean origin. […] Variations in the MEFV gene cause FMF. Your MEFV gene is involved in creating an important protein called pyrin. […] There are at least 30 variations known to cause FMF. The most common ones are V726A, M680I, E148Q, M694V and M694I. […] While familial Mediterranean fever episodes often seem to occur randomly, some people find that physical or emotional stress can trigger an episode. […] Even though episodes of familial Mediterranean fever are temporary, they can take a toll on your body over time. […] Many people carry a gene variant that causes familial Mediterranean fever without realizing it. You need two copies of a variant one from each parent to develop FMF. […] Some researchers believe it may have developed to help fight widespread infections of the time, like tuberculosis.

• #1 Mayo Clinic Health Library – Familial Mediterranean fever | Swiss Medical Network

  https://www.swissmedical.net/en/healtcare-library/con-20372453

  Familial Mediterranean fever is caused by a gene change (mutation) that’s passed from parents to children. The gene change affects the function of an immune system protein called pyrin, causing problems in regulating inflammation in the body. […] In people with FMF, change occurs in a gene called MEFV. Many different changes in MEFV are linked to FMF. Some changes may cause very severe cases, while others may result in milder signs and symptoms. […] It’s unclear what exactly triggers attacks, but they may occur with emotional stress, menstruation, exposure to cold, and physical stress such as illness or injury.

• #1 Familial Mediterranean Fever: Causes, Symptoms, Treatment & More

  https://pharmcourse.com/eu/en/article/view/familial-mediterranean-feve

  Familial Mediterranean Fever (FMF) is a monogenic autoinflammatory disease. […] The MEFV (MEditerranean FeVer) gene: […] responsible for the development of the FMF more than 150 gene variants, mainly missense mutations, less often nonsense mutations, intron mutations, duplications, deletions, and polymorphisms. […] Some patients with symptoms of Mediterranean fever do not have mutations in the MEFV gene. This suggests that other genes may also be involved in the development of the disease. […] The type of inheritance of mutations is autosomal recessive in most cases. […] The pathogenic mechanism in the development of FMF is the hyperproduction of IL-1. […] There are two hypotheses that explain the development of the disease: […] Sequestration hypothesis mutant pyrin cannot suppress the enzyme caspase 1, which is necessary for the conversion of inactive pro-IL-1 into an active form, this leads to IL-1 overproduction and the development of inflammation. […] The pyrine inflammasome hypothesis pyrine is necessary for the formation of an intracellular supramolecular complex involved in the activation of procaspase 1 and thereby stimulating the activity of the IL-1 system.

• #1 Familial Mediterranean fever – Wikipedia

  https://en.wikipedia.org/wiki/Familial_Mediterranean_fever

  The gain-of-function mutations in the MEFV gene cause pyrin to be more active in the body, which increases inflammasome formation. […] It is not conclusively known what exactly sets off the attacks or why overproduction of IL-1 would lead to particular symptoms in particular organs, such as joints or the peritoneal cavity.

• #1 Familial Mediterranean fever: current perspectives | JIR

  https://www.dovepress.com/familial-mediterranean-fever-current-perspectives-peer-reviewed-fulltext-article-JIR

  Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disease, and it is characterized by recurrent attacks of fever and polyserositis. The disease is associated with mutations in the MEFV gene encoding pyrin, which causes exaggerated inflammatory response through uncontrolled production of interleukin 1. […] The gene mutated in patients with FMF is the MEFV gene, which encodes pyrin, which forms an element of the NLRP3 inflammasome complex. Mutations in the MEFV gene are associated with increased interleukin-1 (IL-1), which causes excess inflammation. […] However, it is still controversial whether MEFV mutations cause loss of function or gain of function. […] A recent study by Xu et al has elegantly shown that pyrin is a specific immune sensor for bacterial modifications of Rho GTPases, and responds to Clostridium difficile, which is a frequent cause of nosocomial diarrhea. Pyrin does not directly recognize the microbial products but detects pathogen virulence activity. This recent finding has shed some light on FMF pathogenesis.

• #1 Familial Mediterranean fever: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000363.htm

  Familial Mediterranean fever (FMF) is a rare disorder that may be passed down through families (inherited). It involves repeated fevers and inflammation that often affects the lining of the abdomen, chest, or joints. […] FMF is most often caused by a variation in a gene named MEFV. This gene creates a protein involved in regulating inflammation. The disease usually appears only in people who received two copies of the variant gene, one from each parent. This is called autosomal recessive inheritance or an autosomal recessive condition. […] FMF most often affects people of Mediterranean ancestry. These include non-Ashkenazi (Sephardic) Jews, Armenians, and Arabs. People from other ethnic groups can also be affected.

• #1 Familial Mediterranean Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560754/

  Although predominantly an autosomal recessive disease, some reports of the possible autosomal dominant pattern of transmission have also been described. […] M694V deletion mutation has been the most common mutation found during the analysis of families showing a dominant pattern of transmission of FMF. […] M694V and M680I mutations are associated with the most severe phenotypic expression of FMF with more risk of complications.

• #1 Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7672358/

  The final disease phenotype primarily determined by the MEFV variants carried. […] M694V is the most common and the most penetrant variant causing more pronounced caspase-1, IL-1 family cytokine and S100A12 secretion from neutrophils. […] Patients harbouring biallelic exon 10 variants particularly variants which are homozygous for M694V exhibit a severe disease phenotype characterized by an earlier age of onset, more frequent attacks, musculoskeletal features, lower colchicine response, chronic inflammation, increased risk of comorbid conditions, and disease complications including infertility, joint damage, and secondary amyloidosis. […] Approximately 10%20% of FMF patients in different cohorts do not carry any identified MEFV mutation though it is contentious whether this condition is FMF-like disease or true FMF with as yet unidentified genetic variations. […] The symptoms and severity of FMF can vary among affected individuals with the same MEFV variant, even among members of the same family suggesting contributions by a number of modifiers including other genes, epigenetic and environmental factors.

• #1 Familial Mediterranean fever: Epidemiology, genetics, and pathogenesis – UpToDate

  https://www.uptodate.com/contents/familial-mediterranean-fever-epidemiology-genetics-and-pathogenesis

  Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disorder and is associated with mutations in the MEFV (Mediterranean Fever) gene. […] It is hypothesized that familial Mediterranean fever (FMF) originated more than 3000 years ago in Mesopotamia. […] The evolving geographic reach of FMF is reflected in regional variations in prevalence: […] FMF is most prevalent in individuals of Turkish, Armenian, Middle Eastern, Non-Ashkenazi Jewish, and Arab descent living mainly around the Mediterranean basin. […] In Israel, FMF prevalence varies by ethnic group, ranging from 1 in 500 to 1 in 1000 among non-Ashkenazi Jews, and 1 in 73,000 among Ashkenazi Jews. […] FMF has also been reported at a lower prevalence in many other areas outside the Mediterranean basin and in people with various types of ancestries, including patients in Greece, Italy, Japan, and China. […] In some countries, most patients with FMF have ancestral ties to regions with a higher carrier rate for FMF.

• #1

  https://link.springer.com/article/10.1007/s11739-024-03576-w

  Several possible factors are hypothesized to trigger familial Mediterranean fever (FMF) attacks; however, there is no consensus on this matter. […] The most frequent triggering factor for familial Mediterranean fever attacks was psychological stress (75.2%). Cold exposure was a statistically significant trigger in patients with exon 10 mutations. Humidity was a statistically significant trigger in patients with exon 2 mutations. Seasonal changes, traveling for long durations, relocation, and cold exposure were statistically significant triggers of familial Mediterranean fever attacks in patients with homozygous M694V mutations. Identifying trigger factors can lead to better preventive measures and personalized therapies to decrease familial Mediterranean fever attacks. […] Several factors have been hypothesized to trigger an FMF attack. Possible triggering factors include emotional stress, menstruation, and cold exposure.

• #1

  https://link.springer.com/article/10.1007/s11739-024-03576-w

  Psychological stress, menstruation, and fatigue were among the most common trigger factors in our study and the studies by Karadag et al. and Kishida et al. […] This study shows the high prevalence of triggering factors among patients with FMF. […] Psychological stress and fatigue were the most common triggers of FMF attacks among our patients. Patients can significantly decrease the number of FMF attacks they experience by managing psychological stress and avoiding physical factors such as cold exposure and fatigue. Determining trigger factors and their relationship with patient-specific factors such as mutation status and ethnicity can result in personalized treatment strategies for the prevention of FMF attacks.

• #1 Familial Mediterranean Fever – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/hereditary-periodic-fever-syndromes/familial-mediterranean-fever

  Familial Mediterranean fever (FMF) is caused by mutations in the MEFV gene on the short arm of chromosome 16. […] The mutation is classically inherited in an autosomal recessive manner, but heterozygotes may manifest a clinical phenotype. […] FMF mutations are gain-of-function, that is, they confer new or enhanced activity on a protein, with a gene dosage effect (ie, more copies of the abnormal gene convey a greater effect). […] There is strong evidence that Yersinia pestis, the cause of bubonic plague, led to the positive selection of FMF-associated MEFV mutations. These mutations confer a survival advantage to certain people who harbor Yersinia pestis.

• #1 Familial Mediterranean fever: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/familial-mediterranean-fever/

  Familial Mediterranean fever is caused by variants (also known as mutations) in the MEFV gene. […] Variants in the MEFV gene reduce the activity of the pyrin protein, which disrupts control of the inflammation process. […] Normal variations in the SAA1 gene may modify the course of familial Mediterranean fever. Some evidence suggests that a particular version of the SAA1 gene (called the alpha variant) increases the risk of amyloidosis among people with familial Mediterranean fever.

• #1

  https://journals.lww.com/md-journal/fulltext/2012/05000/familial_mediterranean_fever__risk_factors,_causes.2.aspx

  We assessed the risk factors and causes of death in patients with familial Mediterranean fever (FMF) in an era when colchicine is the standard therapy for all patients. […] The gene responsible for FMF (MEFV) is located on the short arm of chromosome 16 and encodes an immuno-regulatory protein called pyrin. […] The most devastating complication of FMF is amyloid A (AA) protein deposition, which carries with it the potential risk for developing end-stage renal disease. […] In the pre-colchicine era, amyloidosis was the most important prognostic determinant for FMF, since the majority of patients developed amyloidosis before reaching 40 years of age, and only a few patients with FMF survived to the age of 50 years. […] It was recently hypothesized that homozygous or heterozygous MEFV carrier status may provide a selective advantage against contracting certain infectious agents such as tuberculosis.

• #1 Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7672358/

  Familial Mediterranean fever (FMF) is caused by gain of function mutations of MEFV gene which encodes an immune regulatory protein, pyrin. […] FMF results from gain of function mutations of Mediterranean fever gene (MEFV), located on chromosome 16 (16p13.3). […] In FMF, mutations in MEFV gene impair interaction of pyrin with microtubules, PKN and 14-3-3 proteins facilitating formation of a proinflammatory pyrin inflammasome. […] The most common MEFV variant is M694V (c.2080AG) in FMF endemic areas. […] Carriage of these variants is associated with the typical clinical phenotype of FMF and with more severe disease. […] FMF is inherited as autosomal recessive pattern, however approximately 30% of patients harbour single pathogenic variant (monoallelic disease). […] The heterogeneous disease course of FMF results from a complex interplay between genetic and environmental factors.

• #1 New and future perspectives in familial Mediterranean fever and other autoinflammatory diseases | Volume 39 – Issue 3 – September 2024 | Archives of Rheumatology

  https://archivesofrheumatology.org/full-text/1596

  An exciting and current new pathway of autoinflammatory diseases is the trained immune response. […] This reprogramming leads to a stronger inflammatory response to the secondary stimulus through epigenetic changes, such as DNA acetylation and methylation, metabolic pathways, such as glycolysis and cholesterol synthesis, or transcriptional pathways. […] However, it is not yet clear whether trained immunity determines a patient’s sensitivity to a particular treatment. […] Finally, Magnotti et al. showed that steroid hormone catabolites activated pyrin in a B30.2-dependent manner. This data was important since it occurred in the absence of RhoA inhibition, providing a good explanation for why stress triggers FMF attacks.

• #1 New and future perspectives in familial Mediterranean fever and other autoinflammatory diseases | Volume 39 – Issue 3 – September 2024 | Archives of Rheumatology

  https://archivesofrheumatology.org/full-text/1596

  Another exciting development involving the mTOR pathway was the demonstration of the role of mTORC1 signaling in linking the spectrum of inflammation in Still’s disease and macrophage activation syndrome using a combination of model and human studies. […] In both studies, there was a response to rapamycin under experimental conditions. […] In addition, the latter study suggested that the mTORC1 signature in Still’s disease was associated with disease severity and response to treatment. […] Another group studied the mTOR pathway in FMF. […] Receptor-interacting protein kinase 3 was involved in the transcriptional regulation of MEFV through negative control of mTOR signaling, and they showed that the inhibition of mTOR activity upregulated MEFV expression and pyrin inflammasome activation.

• #1 Familial Mediterranean Fever

  https://www.arthritis.org/diseases/familial-mediterranean-fever

  Familial Mediterranean Fever (FMF) is an inherited condition that causes repeated attacks of painful inflammation in the abdomen, chest or joints. […] FMF is caused by mutation in the MEFV gene, which encodes a protein called pyrin found in white blood cells. The mutated protein disrupts the immune system and causes inflammation. […] Researchers think that MEFV gene mutations may be a factor in other autoimmune diseases, including rheumatoid arthritis.

• #1 Familial Mediterranean Fever: Mimics fibromyalgia, arthritis, inflammation

  https://www.geneticlifehacks.com/familial-mediterranean-fever-do-you-carry-the-genetic-variants/

  Results of recent research show that up to 30% of FMF cases are heterozygous (one copy) for a MEFV mutation. […] Researchers theorize that there may be another genetic mutation also involved or environmental factors. […] Research shows that MEFV mutations are found at higher than normal rates in people with the following conditions. […] A study of fibromyalgia patients and their families found that 15% carried heterozygous mutations for familial Mediterranean fever as well as having elevated levels of IL-1B (also found in FMF patients). […] In a study on gouty arthritis, 38% were found to carry an MEFV variant that can cause familial Mediterranean fever. […] A study of lupus patients found that those carrying MEFV variants had an earlier onset of disease, more episodes of fever, and pleurisy.

• #1 Familial Mediteranean Fever (FMF)

  https://www.aiarthritis.org/FMF

  FMF is a genetic disorder that causes repeated episodes of pain and inflammation in the abdomen, chest, joints, and skin, along with fever. […] Autoimmune diseases often run in families, indicating a potential genetic predisposition where that gene can cause disease. Autoinflammatory diseases can occur multiple times in a family, but is based off of genetic mutation. It is not a gene that causes the disease but a mutation on the gene that can cause the disease which can then be passed on to the next generation. […] There’s no single test that can confirm a Familial Mediterranean Fever (FMF) diagnosis, so rheumatologists rely on a combination of physical exams, genetic testing for mutations in the MEFV gene, and family history of autoimmune or autoinflammatory diseases, as well as ethnicity, since FMF is more common in certain populations. While genetic testing for the MEFV mutation is important, the absence of mutations does not completely rule out FMF.

• #1 Familial Mediterranean fever – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/familial-mediterranean-fever/diagnosis-treatment/drc-20372475

  Review of your family medical history. A family history of Familial Mediterranean fever (FMF) increases your likelihood of developing the condition because this genetic change is passed from parents to their children. […] Genetic testing may determine if your MEFV gene contains a gene change that is associated with FMF. Genetic tests aren’t advanced enough to test for every gene change that’s linked to FMF, so there is a possibility of false-negative results. For this reason, health care providers typically don’t use genetic tests as the sole method of diagnosing FMF. […] What caused this condition?

• #1 Familial Mediterranean fever: current perspectives | JIR

  https://www.dovepress.com/familial-mediterranean-fever-current-perspectives-peer-reviewed-fulltext-article-JIR

  The pathogenic role of E148Q on exon 2 (one of the most common alterations in the MEFV gene) still remains controversial. It might be a polymorphism since it is present in 1% of the healthy population. […] The recent evidence-based recommendations for genetic diagnosis of FMF are as follows: FMF is a clinical diagnosis, which can be supported but not excluded by genetic testing. […] The E148Q variant is common, of unknown pathogenic significance, and, as the only MEFV variant, does not support the diagnosis of FMF.

• #1 Familial Mediterranean Fever

  https://www.printo.it/pediatric-rheumatology/IE/info/20/Familial-Mediterranean-Fever

  FMF cannot be cured but it can be treated with life-long use of colchicine. In this way, recurrent attacks can be prevented or decreased and amyloidosis can be prevented. […] If treated properly with life-long colchicine, children with FMF live a normal life. If there is a delay in diagnosis or lack of compliance with treatment, the risk of developing amyloidosis increases, which results in a poor prognosis.

• #1 Infertility Causes and Pregnancy Outcome in Patients With Familial Mediterranean Fever and Controls | The Journal of Rheumatology

  https://www.jrheum.org/content/48/4/608

  Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent attacks of fever and serositis such as peritonitis, pleuritis, synovitis, and pericarditis. Multiple episodes of peritonitis may lead to peritoneal adhesions, which may cause intestinal obstruction and fallopian tube obstruction. One of the main complications of untreated FMF is serum amyloid A amyloidosis. In this condition, amyloid fibers are deposited in kidneys, liver, and intestines, and later may involve the cardiovascular system as well. The gene associated with FMF (MEFV) was isolated in 1997 by 2 independent groups. It is located on the short arm of chromosome 16. The treatment of choice for FMF is colchicine, which is able to control FMF attacks and prevents the development of amyloidosis. However, in vitro studies showed that a high dose of colchicine may affect cell division. Thus, the potential complications of FMF (serosal fibrosis and amyloidosis) and colchicine treatment may affect the reproductive system either by obstruction of the salpinx, causing mechanical infertility, or by defective sperm and oocyte proliferation, leading to difficulties in obtaining pregnancy and normal deliveries.

• #1 Infertility Causes and Pregnancy Outcome in Patients With Familial Mediterranean Fever and Controls | The Journal of Rheumatology

  https://www.jrheum.org/content/48/4/608

  Infertility in patients with FMF was clearly associated with a more severe disease and a lack of adequate colchicine treatment. […] Colchicine medication and controlled FMF disease do not adversely affect the reproductive system and pregnancy outcome. However, a lack of an appropriate colchicine treatment may cause infertility and poor pregnancy outcome. […] Our study results show that the FMF group resembles the FGTB group regarding the etiologies for infertility. However, regarding IVF and pregnancy outcomes, the FMF group more resembles the control group. We observed that FMF has no significant effect on the frequency of early or late abortions, congenital malformations, or late obstetric complications. The slight predominance of early miscarriages and preterm delivery reported by others may be explained by a lack of adequate colchicine treatment. Low SES may also have a similar effect due to a limited access to colchicine and good healthcare. In a recent study, Atas, et al show that FMF disease onset ( 20 years), disease severity, and colchicine nonresponse were independent risk factors for FMF-associated infertility. This observation is in line with our findings and supports the recommendation that patients with FMF should start colchicine immediately at diagnosis and continue treatment even during pregnancy, in order to control the disease and prevent its potential obstetric complications.

• #2 Familial Mediterranean Fever: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/330284-overview

  FMF is a recessive genetic disease associated with missense and nonsense mutations in the MEFV gene, which is located on the short arm of chromosome 16. This gene codes for the protein known as pyrin or marenostrin. […] More than 310 sequence variants in the MEFV gene have been identified, although not all not associated with a disease phenotype. […] Most of the pathogenic mutations are in exon 10 of the gene between amino acids 680 and 761. […] Homozygotes for M694V (valine for methionine at position 694) may experience more severe disease and may be more likely to develop amyloidosis. […] Other genes may be involved in FMF. This possibility is supported by patients who meet criteria for FMF without identifiable mutations in MEFV and who have clinical manifestations that are indistinguishable from patients with MEFV mutations.

• #2 Familial Mediterranean fever – Wikipedia

  https://en.wikipedia.org/wiki/Familial_Mediterranean_fever

  Familial Mediterranean fever (FMF) is a hereditary inflammatory disorder. FMF is an autoinflammatory disease caused by mutations in the Mediterranean fever (MEFV) gene, which encodes a 781 amino acid protein called pyrin. […] Many different mutations of the MEFV gene can cause the disorder. Having one mutation is unlikely to cause the condition. Having two mutations (either a copy from both parents or two different mutations with one from each parent) is the threshold for a genetic diagnosis of FMF, though a minority of clinically-diagnosed cases have only one mutation. […] Virtually all cases are due to a mutation in the Mediterranean Fever (MEFV) gene on the chromosome 16, which codes for a protein called pyrin or marenostrin. Various mutations of this gene lead to FMF, although some mutations cause a more severe picture than others. Mutations occur mainly in exons 2, 3, 5 and 10.

• #2 Familial Mediterranean Fever (FMF): What It Is & Symptoms

  https://my.clevelandclinic.org/health/diseases/familial-mediterranean-fever

  Familial Mediterranean fever (FMF) is a lifelong condition that causes recurring episodes of fever and inflammation throughout your body. Its a genetic disorder that mainly affects people of Mediterranean origin. […] Variations in the MEFV gene cause FMF. Your MEFV gene is involved in creating an important protein called pyrin. […] There are at least 30 variations known to cause FMF. The most common ones are V726A, M680I, E148Q, M694V and M694I. […] While familial Mediterranean fever episodes often seem to occur randomly, some people find that physical or emotional stress can trigger an episode. […] Even though episodes of familial Mediterranean fever are temporary, they can take a toll on your body over time. […] Many people carry a gene variant that causes familial Mediterranean fever without realizing it. You need two copies of a variant one from each parent to develop FMF. […] Some researchers believe it may have developed to help fight widespread infections of the time, like tuberculosis.

• #2 Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7672358/

  Familial Mediterranean fever (FMF) is caused by gain of function mutations of MEFV gene which encodes an immune regulatory protein, pyrin. […] FMF results from gain of function mutations of Mediterranean fever gene (MEFV), located on chromosome 16 (16p13.3). […] In FMF, mutations in MEFV gene impair interaction of pyrin with microtubules, PKN and 14-3-3 proteins facilitating formation of a proinflammatory pyrin inflammasome. […] The most common MEFV variant is M694V (c.2080AG) in FMF endemic areas. […] Carriage of these variants is associated with the typical clinical phenotype of FMF and with more severe disease. […] FMF is inherited as autosomal recessive pattern, however approximately 30% of patients harbour single pathogenic variant (monoallelic disease). […] The heterogeneous disease course of FMF results from a complex interplay between genetic and environmental factors.

• #2 Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7672358/

  The final disease phenotype primarily determined by the MEFV variants carried. […] M694V is the most common and the most penetrant variant causing more pronounced caspase-1, IL-1 family cytokine and S100A12 secretion from neutrophils. […] Patients harbouring biallelic exon 10 variants particularly variants which are homozygous for M694V exhibit a severe disease phenotype characterized by an earlier age of onset, more frequent attacks, musculoskeletal features, lower colchicine response, chronic inflammation, increased risk of comorbid conditions, and disease complications including infertility, joint damage, and secondary amyloidosis. […] Approximately 10%20% of FMF patients in different cohorts do not carry any identified MEFV mutation though it is contentious whether this condition is FMF-like disease or true FMF with as yet unidentified genetic variations. […] The symptoms and severity of FMF can vary among affected individuals with the same MEFV variant, even among members of the same family suggesting contributions by a number of modifiers including other genes, epigenetic and environmental factors.

• #2 Rare Familial Mediterranean Fever

  https://www.webmd.com/arthritis/familial-mediterranean-fever

  Familial Mediterranean fever (FMF) is caused by a mutation in a gene called MEFV. […] Children who have it usually inherit copies of the faulty MEFV gene from both parents. […] There are more than 300 different MEFV mutations, but only a few cause FMF. […] MEFV is a gene that makes a protein called pyrin. Pyrin seems to play a role in how your body’s immune system functions. […] If you have an MEFV gene mutation, your body doesn’t make enough pyrin. As a result, your immune system may make too much of an inflammatory cytokine called interleukin-1B. That causes recurring bouts of inflammation and fevers.

• #2 About Familial Mediterranean Fever

  https://www.genome.gov/Genetic-Disorders/Familial-Mediterranean-Fever

  Familial Mediterranean Fever (FMF) is an inherited disease, characterized by recurrent attacks of fever, inflammation of the abdominal lining (peritonitis), inflammation of the lining surrounding the lungs, painful, swollen joints, and a characteristic ankle rash. […] FMF is considered a rare disease worldwide. However, it is very common in people of Sephardic (non-Ashkenazi) Jewish, Armenian, Arab and Turkish heritage. Among people with these backgrounds, about 1 in 200 has FMF. […] FMF is characterized by relatively short, usually 1- to 3-day, episodes of fever accompanied with serositis, synovitis or skin rash. […] Familial Mediterranean Fever (FMF) is an autosomal recessive inherited disease, which means it appears only in individuals who received two copies of the mutant (altered) gene that causes FMF, one from each parent. […] Located on the short (p) arm of chromosome 16, MEFV (MEditerranean FeVer) is the gene that, when mutated, causes FMF. […] There are more than 30 mutations in the MEFV gene known to cause FMF, but four of them are very common in the patients of Middle Eastern ancestry.

• #2 Familial Mediterranean fever

  https://dermnetnz.org/topics/familial-mediterranean-fever

  Familial Mediterranean fever is usually due to mutations in the Mediterranean fever (MEFV) or pyrin gene located on chromosome 16 (16p13.3). Mutations in the MEFV gene have been found in 80% of typical cases. More than 100 different disease-linked mutations have been identified. The most commonly reported mutation, M694V, is associated with severe disease and the development of secondary amyloidosis. Other common mutations are M680I and V726A. 20% of Ashkenazy Jews carry the E148Q MEFV mutation. […] Familial Mediterranean fever is usually inherited as an autosomal recessive condition, meaning both parents must carry the defective gene and there is a one in four chance of a child being affected (MIM 249100). There is a less common autosomal dominant form (MIM 134610).

• #2 What is Familial Mediterranean Fever? Genetic disorder causes painful inflammation | UCLA Health

  https://www.uclahealth.org/news/article/familial-mediterranean-fever-program

  Familial Mediterranean Fever is an inherited condition that particularly affects those of Arab, Armenian, Jewish, Turkish and other ethnic backgrounds originating in the Mediterranean region. […] It’s most prevalent, due to the high carrier rate, in people of Armenian descent. […] Alexanders genetic test revealed he had characteristic FMF mutations. […] Parents who are healthy, but carriers of the mutation, have a 25% chance of an affected child with each pregnancy. […] The MEFV gene on chromosome 16 codes for the protein pyrin, which is involved in an inflammatory pathway. […] But when the MEFV gene is mutated, it allows the inflammatory reaction to start spontaneously without an infection. […] The neutrophils, a type of white blood cell, start multiplying and releasing cytokines. […] You can get a cytokine storm where the body itself is causing a lot of pain and misery. […] We don’t actually know why those white blood cells start this and why it’s on a cycle.

• #2 Familial Mediterranean fever is no longer a rare disease in Italy | European Journal of Human Genetics

  https://www.nature.com/articles/5200916

  The following results, drawn from geno-phenotypical correlations, are similar to those of other authors: (a) M694V and M680I homozygotes and any type of compound heterozygotes at these two codons confirmed their association with a severe phenotype. […] Genetically, she is the patient with the first non-sense, probably dominant MEFV mutation. […] Our results confirm the conclusions of A. Piazza, which stated that, before Roman domination, 1/1015 inhabitants of Italy had Greek ancestry. […] Are there some specific Italian mutations? Or are they the sum of the single amounts of unknown mutations of the different ancient Mediterranean peoples from whom they derive? […] In conclusion, we demonstrated and genetically confirmed that FMF does exist in Italy and is frequently undiagnosed or a long delay precedes the diagnosis.

• #2 Familial Mediterranean fever (FMF) | Sobi

  https://www.sobi.com/en/familial-mediterranean-fever-fmf

  FMF is not contagious. And is not considered idiopathic meaning that it can’t occur spontaneously. FMF is hereditary, not acquired. The disease is mostly passed on in an autosomal recessive fashion. […] Episodes of FMF can occur with no identifiable trigger. But certain triggers have been identified in some cases. Triggers include infection, trauma, vigorous exercise, stress, and fatigue. In women, onset of their period can trigger an episode.

• #2

  https://link.springer.com/article/10.1007/s11739-024-03576-w

  Psychological stress, menstruation, and fatigue were among the most common trigger factors in our study and the studies by Karadag et al. and Kishida et al. […] This study shows the high prevalence of triggering factors among patients with FMF. […] Psychological stress and fatigue were the most common triggers of FMF attacks among our patients. Patients can significantly decrease the number of FMF attacks they experience by managing psychological stress and avoiding physical factors such as cold exposure and fatigue. Determining trigger factors and their relationship with patient-specific factors such as mutation status and ethnicity can result in personalized treatment strategies for the prevention of FMF attacks.

• #2 Familial Mediterranean Fever: Mimics fibromyalgia, arthritis, inflammation

  https://www.geneticlifehacks.com/familial-mediterranean-fever-do-you-carry-the-genetic-variants/

  The familial Mediterranean fever mutations in MEFV cause malformation in pyrin that then causes less control of inflammation. […] Researchers have found that people with familial Mediterranean fever mutations do have a positive trade-off: resistance to Yersinia pestis, the bacteria that causes the plague.

• #2 Familial Mediterranean Fever: Causes, Diagnosis, and Treatment

  https://www.verywellhealth.com/familial-mediterranean-fever-4159712

  Familial Mediterranean fever (FMF) is a rare genetic disorder that is primarily seen in some ethnic populations. […] The disease is associated with mutations in the Mediterranean fever (MEFV) gene, of which there are more than 30 variations. […] With FMF, the MEFV mutation almost always affects chromosome 16. […] Of the 30-plus variations of the MEFV mutation, there are four that are closely linked to symptomatic disease. […] Because there are well over 30 variations of the MEFV mutation, different recessive combinations can end up meaning vastly different things. […] Variations of the MEFV mutation have been traced back as far as biblical times when Jewish sailors began the migration from Southern Europe to North Africa and the Middle East.

• #2 Familial Mediterranean fever | EBSCO Research Starters

  https://www.ebsco.com/research-starters/health-and-medicine/familial-mediterranean-fever

  The FMF gene mutation may alter the pyrin molecule in such a way that it fails to suppress unknown triggers in the inflammatory response, resulting in spontaneous episodes of neutrophil-predominant inflammation. […] FMF is almost always inherited in an autosomal recessive pattern. […] In addition to the MEFV gene mutation, normal variations in the SAA1 gene, which encodes the serum amyloid A1 protein, may influence the course of FMF. A version of the SAA1 gene called the alpha variant may increase the risk of developing amyloidosis in some people with FMF.

• #2

  https://journals.lww.com/md-journal/fulltext/2012/05000/familial_mediterranean_fever__risk_factors,_causes.2.aspx

  Although factors influencing the development of amyloidosis in patients with FMF have been investigated in the past few decades, to our knowledge factors influencing overall FMF patient mortality have not been evaluated in the colchicine era. […] The most serious complication of FMF is AA amyloidosis. […] The underlying basis for AA fibril deposition in FMF remains largely unknown. […] Development of amyloidosis has been shown to be associated with certain MEFV mutations, family history of amyloidosis, and male sex. […] Following the discovery of the MEFV gene, numerous studies evaluated possible genotype-phenotype correlations in FMF. […] The MEFV M694V mutation has been associated with renal amyloidosis in FMF patients of Armenian, Jewish, and Arabic heritage. […] However, most studies conducted in Turkey, including the current study, did not confirm this association.

• #2 Familial Mediterranean fever—A review | Genetics in Medicine

  https://www.nature.com/articles/gim9201181

  Disagreement exists as to whether p.Glu148Gln is a mutation or simply a polymorphism; p.Glu148Gln is predominant in Ashkenazi and Iraqi Jews, Armenians, and Turks and has been found to be associated with a generally mild form of FMF. […] Several studies describe p.Glu148Gln as a disease-causing mutation. […] New studies have cast considerable doubt on whether FMF is, in fact, a traditional autosomal recessive disease. […] Another suggestion is the coexistence of another autoinflammatory disease, which would have to be carefully excluded. […] The final possibility suggested is the effect of environment.

• #2 Familial Mediterranean Fever Bangalore | Arthritis Foundation of Asia

  https://www.arthritisfoundationasia.com/familial-mediterranean-fever.html

  Familial Mediterranean fever is caused by mutation in the MEVV gene, which encodes a protein called pyrin found in white blood cells. The mutated protein causes disruptions in control of the immune system, which leads to misguided or lingering inflammation. […] Some studies suggest that MEVV gene mutations are also associated with other autoimmune diseases, including rheumatoid arthritis.

• #2 Familial Mediterranean fever – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/familial-mediterranean-fever/diagnosis-treatment/drc-20372475

  Review of your family medical history. A family history of Familial Mediterranean fever (FMF) increases your likelihood of developing the condition because this genetic change is passed from parents to their children. […] Genetic testing may determine if your MEFV gene contains a gene change that is associated with FMF. Genetic tests aren’t advanced enough to test for every gene change that’s linked to FMF, so there is a possibility of false-negative results. For this reason, health care providers typically don’t use genetic tests as the sole method of diagnosing FMF. […] What caused this condition?

• #2 Familial Mediteranean Fever (FMF)

  https://www.aiarthritis.org/FMF

  FMF is a genetic disorder that causes repeated episodes of pain and inflammation in the abdomen, chest, joints, and skin, along with fever. […] Autoimmune diseases often run in families, indicating a potential genetic predisposition where that gene can cause disease. Autoinflammatory diseases can occur multiple times in a family, but is based off of genetic mutation. It is not a gene that causes the disease but a mutation on the gene that can cause the disease which can then be passed on to the next generation. […] There’s no single test that can confirm a Familial Mediterranean Fever (FMF) diagnosis, so rheumatologists rely on a combination of physical exams, genetic testing for mutations in the MEFV gene, and family history of autoimmune or autoinflammatory diseases, as well as ethnicity, since FMF is more common in certain populations. While genetic testing for the MEFV mutation is important, the absence of mutations does not completely rule out FMF.

• #2 Familial Mediterranean fever: current perspectives | JIR

  https://www.dovepress.com/familial-mediterranean-fever-current-perspectives-peer-reviewed-fulltext-article-JIR

  Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disease, and it is characterized by recurrent attacks of fever and polyserositis. The disease is associated with mutations in the MEFV gene encoding pyrin, which causes exaggerated inflammatory response through uncontrolled production of interleukin 1. […] The gene mutated in patients with FMF is the MEFV gene, which encodes pyrin, which forms an element of the NLRP3 inflammasome complex. Mutations in the MEFV gene are associated with increased interleukin-1 (IL-1), which causes excess inflammation. […] However, it is still controversial whether MEFV mutations cause loss of function or gain of function. […] A recent study by Xu et al has elegantly shown that pyrin is a specific immune sensor for bacterial modifications of Rho GTPases, and responds to Clostridium difficile, which is a frequent cause of nosocomial diarrhea. Pyrin does not directly recognize the microbial products but detects pathogen virulence activity. This recent finding has shed some light on FMF pathogenesis.

• #2 Infertility Causes and Pregnancy Outcome in Patients With Familial Mediterranean Fever and Controls | The Journal of Rheumatology

  https://www.jrheum.org/content/48/4/608

  Infertility in patients with FMF was clearly associated with a more severe disease and a lack of adequate colchicine treatment. […] Colchicine medication and controlled FMF disease do not adversely affect the reproductive system and pregnancy outcome. However, a lack of an appropriate colchicine treatment may cause infertility and poor pregnancy outcome. […] Our study results show that the FMF group resembles the FGTB group regarding the etiologies for infertility. However, regarding IVF and pregnancy outcomes, the FMF group more resembles the control group. We observed that FMF has no significant effect on the frequency of early or late abortions, congenital malformations, or late obstetric complications. The slight predominance of early miscarriages and preterm delivery reported by others may be explained by a lack of adequate colchicine treatment. Low SES may also have a similar effect due to a limited access to colchicine and good healthcare. In a recent study, Atas, et al show that FMF disease onset ( 20 years), disease severity, and colchicine nonresponse were independent risk factors for FMF-associated infertility. This observation is in line with our findings and supports the recommendation that patients with FMF should start colchicine immediately at diagnosis and continue treatment even during pregnancy, in order to control the disease and prevent its potential obstetric complications.

• #3 Familial Mediterranean fever – Wikipedia

  https://en.wikipedia.org/wiki/Familial_Mediterranean_fever

  Familial Mediterranean fever (FMF) is a hereditary inflammatory disorder. FMF is an autoinflammatory disease caused by mutations in the Mediterranean fever (MEFV) gene, which encodes a 781 amino acid protein called pyrin. […] Many different mutations of the MEFV gene can cause the disorder. Having one mutation is unlikely to cause the condition. Having two mutations (either a copy from both parents or two different mutations with one from each parent) is the threshold for a genetic diagnosis of FMF, though a minority of clinically-diagnosed cases have only one mutation. […] Virtually all cases are due to a mutation in the Mediterranean Fever (MEFV) gene on the chromosome 16, which codes for a protein called pyrin or marenostrin. Various mutations of this gene lead to FMF, although some mutations cause a more severe picture than others. Mutations occur mainly in exons 2, 3, 5 and 10.

• #3 About Familial Mediterranean Fever

  https://www.genome.gov/Genetic-Disorders/Familial-Mediterranean-Fever

  Familial Mediterranean Fever (FMF) is an inherited disease, characterized by recurrent attacks of fever, inflammation of the abdominal lining (peritonitis), inflammation of the lining surrounding the lungs, painful, swollen joints, and a characteristic ankle rash. […] FMF is considered a rare disease worldwide. However, it is very common in people of Sephardic (non-Ashkenazi) Jewish, Armenian, Arab and Turkish heritage. Among people with these backgrounds, about 1 in 200 has FMF. […] FMF is characterized by relatively short, usually 1- to 3-day, episodes of fever accompanied with serositis, synovitis or skin rash. […] Familial Mediterranean Fever (FMF) is an autosomal recessive inherited disease, which means it appears only in individuals who received two copies of the mutant (altered) gene that causes FMF, one from each parent. […] Located on the short (p) arm of chromosome 16, MEFV (MEditerranean FeVer) is the gene that, when mutated, causes FMF. […] There are more than 30 mutations in the MEFV gene known to cause FMF, but four of them are very common in the patients of Middle Eastern ancestry.

• #3 Familial Mediterranean Fever: Causes, Symptoms, Treatment & More

  https://pharmcourse.com/eu/en/article/view/familial-mediterranean-feve

  Familial Mediterranean Fever (FMF) is a monogenic autoinflammatory disease. […] The MEFV (MEditerranean FeVer) gene: […] responsible for the development of the FMF more than 150 gene variants, mainly missense mutations, less often nonsense mutations, intron mutations, duplications, deletions, and polymorphisms. […] Some patients with symptoms of Mediterranean fever do not have mutations in the MEFV gene. This suggests that other genes may also be involved in the development of the disease. […] The type of inheritance of mutations is autosomal recessive in most cases. […] The pathogenic mechanism in the development of FMF is the hyperproduction of IL-1. […] There are two hypotheses that explain the development of the disease: […] Sequestration hypothesis mutant pyrin cannot suppress the enzyme caspase 1, which is necessary for the conversion of inactive pro-IL-1 into an active form, this leads to IL-1 overproduction and the development of inflammation. […] The pyrine inflammasome hypothesis pyrine is necessary for the formation of an intracellular supramolecular complex involved in the activation of procaspase 1 and thereby stimulating the activity of the IL-1 system.

• #3 Familial Mediterranean fever: current perspectives | JIR

  https://www.dovepress.com/familial-mediterranean-fever-current-perspectives-peer-reviewed-fulltext-article-JIR

  Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disease, and it is characterized by recurrent attacks of fever and polyserositis. The disease is associated with mutations in the MEFV gene encoding pyrin, which causes exaggerated inflammatory response through uncontrolled production of interleukin 1. […] The gene mutated in patients with FMF is the MEFV gene, which encodes pyrin, which forms an element of the NLRP3 inflammasome complex. Mutations in the MEFV gene are associated with increased interleukin-1 (IL-1), which causes excess inflammation. […] However, it is still controversial whether MEFV mutations cause loss of function or gain of function. […] A recent study by Xu et al has elegantly shown that pyrin is a specific immune sensor for bacterial modifications of Rho GTPases, and responds to Clostridium difficile, which is a frequent cause of nosocomial diarrhea. Pyrin does not directly recognize the microbial products but detects pathogen virulence activity. This recent finding has shed some light on FMF pathogenesis.

• #3 Familial Mediterranean Fever

  https://www.printo.it/pediatric-rheumatology/IE/info/20/Familial-Mediterranean-Fever

  Familial Mediterranean Fever (FMF) is a genetically transmitted disease. […] FMF is a genetic disease. The responsible gene is called the MEFV gene and it affects a protein that plays a role in the natural resolution of inflammation. If this gene carries a mutation, as it does in FMF, this regulation cannot function properly and patients experience attacks of fever. […] It is mostly inherited as an autosomal recessive disease, which means that parents usually do not show symptoms of the disease. This type of transmission means that to have FMF, both copies of the MEFV gene in an individual (one from the mother and the other from the father) are mutated; hence, both parents are carriers (a carrier has only one mutated copy but not the disease). […] Your child has the disease because they have a fault (mutation) in the gene that causes FMF.

• #3 Familial Mediterranean fever is no longer a rare disease in Italy | European Journal of Human Genetics

  https://www.nature.com/articles/5200916

  The following results, drawn from geno-phenotypical correlations, are similar to those of other authors: (a) M694V and M680I homozygotes and any type of compound heterozygotes at these two codons confirmed their association with a severe phenotype. […] Genetically, she is the patient with the first non-sense, probably dominant MEFV mutation. […] Our results confirm the conclusions of A. Piazza, which stated that, before Roman domination, 1/1015 inhabitants of Italy had Greek ancestry. […] Are there some specific Italian mutations? Or are they the sum of the single amounts of unknown mutations of the different ancient Mediterranean peoples from whom they derive? […] In conclusion, we demonstrated and genetically confirmed that FMF does exist in Italy and is frequently undiagnosed or a long delay precedes the diagnosis.

• #3

  https://journals.lww.com/md-journal/fulltext/2012/05000/familial_mediterranean_fever__risk_factors,_causes.2.aspx

  Although factors influencing the development of amyloidosis in patients with FMF have been investigated in the past few decades, to our knowledge factors influencing overall FMF patient mortality have not been evaluated in the colchicine era. […] The most serious complication of FMF is AA amyloidosis. […] The underlying basis for AA fibril deposition in FMF remains largely unknown. […] Development of amyloidosis has been shown to be associated with certain MEFV mutations, family history of amyloidosis, and male sex. […] Following the discovery of the MEFV gene, numerous studies evaluated possible genotype-phenotype correlations in FMF. […] The MEFV M694V mutation has been associated with renal amyloidosis in FMF patients of Armenian, Jewish, and Arabic heritage. […] However, most studies conducted in Turkey, including the current study, did not confirm this association.

• #3 Familial Inheritance: Familial Mediterranean Fever – Anatolia Geneworks

  https://www.anatoliageneworks.com/news/familial-inheritance-familial-mediterranean-fever/

  Familial Mediterranean Fever is a genetic disease that is more common in people living in the Mediterranean region, i.e. people of Turkish, Arab, Armenian, Jewish, Italian, Greek and Spanish descent. The disease is caused by mutations (permanent changes) in a gene called MEFV. This gene is responsible for the production of a protein called pyrin, which is responsible for the inflammatory response. As a result of this mutation in the MEFV gene, the pyrin protein cannot function properly and causes irregularities in inflammation processes. This leads to the development of autoinflammatory symptoms characteristic of this disease. […] The main reason why the disease is often seen in Mediterranean countries is its hereditary characteristic. […] The three most common mutations in the MEFV gene are M694V (51%), M680I (14%), and V726A (9%).

• #3 Mayo Clinic Health Library – Familial Mediterranean fever | Swiss Medical Network

  https://www.swissmedical.net/en/healtcare-library/con-20372453

  Familial Mediterranean fever is caused by a gene change (mutation) that’s passed from parents to children. The gene change affects the function of an immune system protein called pyrin, causing problems in regulating inflammation in the body. […] In people with FMF, change occurs in a gene called MEFV. Many different changes in MEFV are linked to FMF. Some changes may cause very severe cases, while others may result in milder signs and symptoms. […] It’s unclear what exactly triggers attacks, but they may occur with emotional stress, menstruation, exposure to cold, and physical stress such as illness or injury.

• #3

  https://journals.lww.com/md-journal/fulltext/2012/05000/familial_mediterranean_fever__risk_factors,_causes.2.aspx

  We assessed the risk factors and causes of death in patients with familial Mediterranean fever (FMF) in an era when colchicine is the standard therapy for all patients. […] The gene responsible for FMF (MEFV) is located on the short arm of chromosome 16 and encodes an immuno-regulatory protein called pyrin. […] The most devastating complication of FMF is amyloid A (AA) protein deposition, which carries with it the potential risk for developing end-stage renal disease. […] In the pre-colchicine era, amyloidosis was the most important prognostic determinant for FMF, since the majority of patients developed amyloidosis before reaching 40 years of age, and only a few patients with FMF survived to the age of 50 years. […] It was recently hypothesized that homozygous or heterozygous MEFV carrier status may provide a selective advantage against contracting certain infectious agents such as tuberculosis.

• #3 Familial Mediterranean Fever: Mimics fibromyalgia, arthritis, inflammation

  https://www.geneticlifehacks.com/familial-mediterranean-fever-do-you-carry-the-genetic-variants/

  Results of recent research show that up to 30% of FMF cases are heterozygous (one copy) for a MEFV mutation. […] Researchers theorize that there may be another genetic mutation also involved or environmental factors. […] Research shows that MEFV mutations are found at higher than normal rates in people with the following conditions. […] A study of fibromyalgia patients and their families found that 15% carried heterozygous mutations for familial Mediterranean fever as well as having elevated levels of IL-1B (also found in FMF patients). […] In a study on gouty arthritis, 38% were found to carry an MEFV variant that can cause familial Mediterranean fever. […] A study of lupus patients found that those carrying MEFV variants had an earlier onset of disease, more episodes of fever, and pleurisy.

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