Genotype-phenotype relation of NLPR3 genetic mutations or polymorphisms

Inflammomas are an essential part of the natural immune response and are multiple intracellular protein complexes that severely control different aspects of adaptive immunity. Generally, sensory molecules recognize different pathogenic (PAMP) or endogenous sterile distress signals (DAMP) they activate caspase-1 using adapter proteins such as ASC, leading to the processing and release of pro-inflammatory cytokines such as interleukin (IL) -1β and IL-18. 7 different, the inflammasome is known among my most researched NLRP3 inflammasome pathway. It is known that mutations detected in the NLRP3 gene, which encodes the sensor protein chryphoria, are caused by 3 different diseases. In this study, it was aimed to evaluate the DNA variants and protein structure obtained by NLRP3 gene analysis in patients with clinically and laboratory findings specific for autoinflammatory disease and negative MEFV and MVK gene mutations, and to investigate its reflection on the phenotype. For this purpose, a total of 50 people, 25 of which are healthy and 25 of which are working groups, were taken into employment. Mutagenesis was performed by sanger DNA sequencing methods and results were read by Finch TV, CLC Sequence Viewer - QIAGEN Bioinformatics and MEGA7 biomorphological porograms. Mortality evaluations were done according to NCBI, PolyPhen-2, INFEVERS and many different databases. Consequently, control and two study groups (Ala240Ala and Arg260Arg) synonymous amino acid mutations were identified and evaluated with no phenotype poyimorfizm as to whether there is a relationship. In addition, two individuals in the study group did not have a mutation in the Intron-Exon sequence screening and it is estimated that other genes associated with the genetic genetic autoinflammatory disease were affected. There was no disease-related mutation in the control group. Seven different mutations were identified in the study group, which were reported to the INFEVERS database for the first time as a Thr913Met mutation. The effect of each mutation on protein structure was further investigated. Consequently, in this thesis, NLRP3 gene analysis was performed in patients with both healthy and autoinflamatory clinical and laboratory findings and the causative genetic variants of the disease were determined and protein effects were determined.