Inflammation Genetics Genome Periodic fever syn Family Video FM TV

Disease Genetics

Periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome is an autoinflammatory disease whose genetic basis has been assumed. However, compared with other periodic fever syndromes, no candidate genes have been found. Through cloning, long insert size paired-end sequencing, de novo chromosomal translocation t (10; 17) (q11.2; p13) in patients with typical PFAPA syndrome lacks gene mutations associated with other periodic fever syndromesFamily Video, We identified SPAG7 as a candidate gene for PFAPA. SPAG7 protein is expressed in tissues affected by PFAPA and is functionally related to antiviral and inflammatory responses. Due to the microdeletion at the translocation break, the loss of exons 2-7 of one allele leads to the haploinsufficiency of SPAG7 which is related to PFAPA in the index. Sequence analysis of SPAG7 in other PFAPA patients points to alternative mechanisms of genetic heterogeneity or SPAG7 dysregulation, such as somatic or epigenetic changes.


Periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome are autoinflammatory diseases described for the first time by Marshall et al. It is characterized by fever lasting 3-6 days, recurrence every 3-8 weeks, exudative tonsillitis, cervical adenopathy and discomfort in all patients and aphthous in most patients. 2, 3, 4, 5 Headache, abdominal pain and joint pain were also observed repeatedly.

Although there is currently a lack of candidate genes for PFAPA syndrome, various studies have shown that this autoinflammatory disease is not a sporadic disease, but is based on genetic susceptibility. 8 The main epidemiological evidence for this hypothesis comes from the observations of Cochard et al. 9 These authors show that a significant proportion of PFAPA patients exhibit a general family history of recurrent fever, especially PFAPA. In fact, in this study, 10 out of 84 (12%) patients had PFAPA syndrome. Even in 84 (45%) patients, 38 had a family history of recurrent fever.FM TV The high frequency of recurrent fever other than PFAPA among 9 patients’ family members is consistent with the observation that PFAPA syndrome patients are more likely to have heterozygous mutation carriers in genes related to other familial periodic fever. Syndromes. In particular, heterozygous mutations in the MEFV gene associated with FMF are common in PFAPA patients. This MEFV mutation may change the clinical course of the disease. 11

Overall, despite the significant family clustering, molecular data and the lack of clear single-gene traits may point to the polygenic or multi-factor origin of PFAPA, rather than single-gene susceptibility. Part of this susceptibility may be conferred by inflammasome-related genes such as sequence variants in NLRP3. This has been described in about 20% of PFAPA patients. These variants may increase the possibility of dysregulation of interleukin 1β production by monocytes during typical fever in PFAPA syndrome. Overall, the functional studies published to date point to a pathophysiological model of PFAPA syndrome, in which microbial-triggered activation begins with the innate immune system and eventually recruits activated T cells to the periphery. Therefore, PFAPA syndrome may be due to an abnormal adaptive immune response to viruses or other infectious agents, which may induce rapid activation of innate immune cells at the level of lymphoid organs. 8, 13 This hypothesis of the source of infection at the level of lymphoid organs is consistent with the histological findings of tonsils in patients with PFAPA syndrome. PFAPA syndrome shows non-specific chronic inflammation, which is characterized by lymphoid and follicular immunoblast proliferation and focal histiocytes. Masses, hyaline fibrosis, crypt abscesses and keratinized fragments. 14

It has recently been shown that cloning the breakpoint of de novo balanced chromosomal translocation in patients with phenotypic abnormalities of unknown origin can lead to the identification of disease-causing genes. 15, 16 We have applied this strategy to PFAPA and described the breakpoint of de novo chromosomal translocation in a patient with PFAPA syndrome who has no family history of recurrent fever and lacks mutations in known genes associated with recurrent fever syndrome , And massively use parallel DNA sequencing.USA Funny Video, Through this method, we identified SPAG7 as a new candidate gene for PFAPA syndrome in this article. It was found that the SPAG7 gene in patients was de novo haploinsufficient, the expression of SPAG7 protein in tonsils and lymph nodes, and the evidence of its involvement in antiviral and inflammatory responses were completely consistent with the above models. Pathogenesis of PFAPA.

Results and discussion

To determine the underlying genetic cause of PFAPA syndrome, we investigated whether any patients with this autoinflammation present in our institution were diagnosed with chromosomal aberrations. Using this method, we identified a girl with typical clinical features of PFAPA syndrome. Before this diagnosis, due to growth retardation, facial abnormalities and developmental abnormalities of brachymesophalangy V, chromosome analysis of peripheral blood lymphocytes (detailed See the clinical summary of materials and methods for the clinical description). The 400-based G-banding karyotype analysis showed that there was a cytogenetic balanced translocation between the long arm of chromosome 10 and the short arm of chromosome 17 in the metaphase of all 20 analyses (Figure 1). The karyotype is described as: 46, XX, t(10; 17) (q11.2; p13). It is worth noting that the chromosomal analysis of the peripheral blood of the parents revealed the normal karyotypes of the mother and father. Therefore, t(10; 17) is the patient’s de novo event. Given that both parents are generally healthy, especially with neither signs of PFAPA syndrome nor any other reported autoimmune or autoinflammatory diseases, the reappearance of PFAPA syndrome and translocation may indicate a causal relationship. In fact, it has been shown that carriers of de novo balanced chromosomal rearrangements have a two to three-fold increase in the risk of congenital abnormalities. 15, 17 Therefore, this de novo balanced chromosomal rearrangement breakpoint that cloned patients with phenotypic abnormalities of unknown origin has been successfully used to identify disease-causing genes. 15, 16

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