|
|
Mechanisms of immune dysregulation leading to inflammatory bowel disease
Horáčková, Klára ; Froňková, Eva (advisor) ; Filipp, Dominik (referee)
Bc. Klára Horáčková DIPLOMA THESIS Mechanisms of immune dysregulation leading to inflammatory bowel disease Abstract Inflammatory bowel disease (IBD) is a complex disorder characterized by chronic inflammation of the gastrointestinal tract. Classical IBD is a multifactorial disease with adulthood or later-childhood onset. However, children with very early onset IBD (VEO-IBD, before 6 years of age) are a specific cohort, whose pathology can be caused by severe genetic defects in genes connected to immune homeostasis in the gut. We aimed to identify the causal genetic variants in 20 pediatric patients diagnosed with IBD (age of onset from 3 to 154 months) using whole exome sequencing (WES). We evaluated several bioinformatical approaches for WES data analysis. This included a comparison of two methods of variant identification using VarScan2 or GATK4-based tools. Furthermore, we compared 4 gene lists ("virtual panels") for variant filtering, one of which was compiled purposefully for this thesis. We identified and validated via segregation analysis 5 causal variants in 4 genes (DUOX2 compound heterozygote, FOXP3, NLRP3 and NOD2) accounting for 20 % of the cohort. NOD2 (p.A755V) variant has already been reported in IBD cases, while DUOX2 (p.R1216W + p.A1131T), FOXP3 (p.H400L) and NLRP3 (p.V200M) were newly...
|
|
| |
|
|
Mechanisms of immune dysregulation leading to inflammatory bowel disease
Horáčková, Klára ; Froňková, Eva (advisor) ; Filipp, Dominik (referee)
Bc. Klára Horáčková DIPLOMA THESIS Mechanisms of immune dysregulation leading to inflammatory bowel disease Abstract Inflammatory bowel disease (IBD) is a complex disorder characterized by chronic inflammation of the gastrointestinal tract. Classical IBD is a multifactorial disease with adulthood or later-childhood onset. However, children with very early onset IBD (VEO-IBD, before 6 years of age) are a specific cohort, whose pathology can be caused by severe genetic defects in genes connected to immune homeostasis in the gut. We aimed to identify the causal genetic variants in 20 pediatric patients diagnosed with IBD (age of onset from 3 to 154 months) using whole exome sequencing (WES). We evaluated several bioinformatical approaches for WES data analysis. This included a comparison of two methods of variant identification using VarScan2 or GATK4-based tools. Furthermore, we compared 4 gene lists ("virtual panels") for variant filtering, one of which was compiled purposefully for this thesis. We identified and validated via segregation analysis 5 causal variants in 4 genes (DUOX2 compound heterozygote, FOXP3, NLRP3 and NOD2) accounting for 20 % of the cohort. NOD2 (p.A755V) variant has already been reported in IBD cases, while DUOX2 (p.R1216W + p.A1131T), FOXP3 (p.H400L) and NLRP3 (p.V200M) were newly...
|
|
|
Crohn's disease exclusive enteral nutrition treatment during childhood
Černá, Martina ; Starnovská, Tamara (advisor) ; El-Lababidi, Nabil (referee)
This bachelor thesis focuses on the problems of Crohn's disease and its treatment with exclusive enteral nutrition in childhood. The thesis is divided into two parts - theoretical and practical. The basic facts about epidemiology, etiopathogenesis, symptoms, diagnostics, diet, treatment and the specifics of Crohn's disease in childhood are given in the theoretical part. The practical part looks at the five casuistries of children suffering from Crohn's disease and treated with exclusive enteral nutrition. The goal of this work was to compare the information from literature and furthermore evaluate the health conditions before and after the treatment.
|
guest ::
