Evaluation of microarray and whole exome sequencing analysis data in pediatric-onset inflammatory bowel disease cases

Inflammatory bowel disease (IBD) is a multifactorial disease characterized by chronic, relapsing inflammation of the gastrointestinal tract. While genetic factors in IBD pathogenesis are mostly polygenic, monogenic diseases have been identified, particularly in patients with very early-onset IBD (0–6 years) or atypical/aggressive clinical presentations. This study aimed to investigate monogenic causes underlying pediatric-onset IBD. A total of 22 patients [13 female (59.1%) and 9 male (40.9%)] were included in the study among 130 IBD patients followed up in Eskişehir Osmangazi University Pediatric Gastroenterology and Hepatology Department between 2016-2023. Of these patients, 16 had early-onset IBD (0–10 years), and 6 had later (>10 years) onset with atypical clinical features, refractory disease or a family history of IBD. The median age of IBD onset was 7.5 years (IQR 5-11.5). Among the cases, 45,5% (10/22) were diagnosed with ulcerative colitis, 31,8% (7/22) with unclassified IBD, and 22,7% (5/22) with Crohn's disease. Whole exome sequencing (WES) and microarray data of all cases were analyzed. IBD related monogenic diseases were identified in 27,3% (6/22) of cases through WES analysis. Three cases were diagnosed with familial Mediterranean fever, one with CARMIL2 deficiency, one with XIAP deficiency, and one with prolidase deficiency and TACI deficiency. Variants of uncertain clinical significance in IBD-related or candidate genes, potentially contributing to IBD pathogenesis, were identified in eight cases (36,4%). No clinically relevant copy number variations were detected through microarray analysis. Early genetic diagnosis provides valuable prognostic insights and facilitates personalized therapeutic strategies, potentially improving the management of pediatric IBD patients. This study underscores the importance of WES analysis in identifying monogenic etiologies, particularly in patients with very early-onset or aggressive forms of IBD.