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. 2025 Apr 23;12(5):536.
doi: 10.3390/children12050536.

Genetic Variants in Early-Onset Inflammatory Bowel Disease: Monogenic Causes and Clinical Implications

Duygu Demirtas Guner  1 , Hacer Neslihan Bildik  2 , Hulya Demir  1 , Deniz Cagdas  3 , Inci Nur Saltik Temizel  1 , Riza Koksal Ozgul  4 , Hayriye Hizarcioglu Gulsen  1 , Cagman Tan  2 , Begum Cicek  2 , Hasan Ozen  1 , Aysel Yuce  1 , Ilhan Tezcan  3
Affiliations

Genetic Variants in Early-Onset Inflammatory Bowel Disease: Monogenic Causes and Clinical Implications

Duygu Demirtas Guner et al. Children (Basel). .

Abstract

Background/Objectives: This study aims to identify genetic variants associated with early-onset inflammatory bowel disease (IBD) and to improve diagnostic and therapeutic approaches. In selected monogenic IBD cases, treatment included colchicine, interleukin-1 inhibitors, and hematopoietic stem cell transplantation. Methods: This study included patients with early-onset IBD, defined as IBD diagnosed before the age of 10, who were under follow-up at the Department of Pediatric Gastroenterology, Hacettepe University, and agreed to participate between December 2018 and April 2021. Whole-exome sequencing (WES) was performed prospectively in patients without a prior diagnosis of monogenic disease, while clinical and laboratory data were reviewed retrospectively. Identified variants were evaluated for pathogenicity using standard bioinformatics tools. Results: A total of 47 patients were enrolled, including 33 boys (70.2%) and 14 girls (29.8%). The median age at symptom onset was 36 months (IQR: 10-72), and the median age at diagnosis was 3.7 years (IQR: 1.5-7.6). Crohn's disease was diagnosed in 53.2% (n = 25), ulcerative colitis in 38.3% (n = 18), and unclassified IBD in 8.5% (n = 4). Monogenic IBD was identified in 36.2% (n = 17) of patients, including nine with Familial Mediterranean Fever and others with glycogen storage disease type 1b (n = 2), XIAP deficiency, chronic granulomatous disease, DOCK8 deficiency, IL10 receptor alpha defect, LRBA deficiency, and NFKB2 deficiency (n = 1 each). A novel SLC29A3 gene variant (c.480_481delTGinsCA, p.V161I) (transcript ID: ENST00000479577.2) was identified in 76.6% (n = 36) of patients. Conclusions: This study underscores the importance of genetic variants in early-onset IBD, particularly MEFV and the novel NFKB2. The frequent detection of the SLC29A3 variant may suggest its potential involvement in the pathogenesis of the disease.

Keywords: Inflammatory bowel diseases; MEFV; NFKB2; SLC29A3; monogenic diseases; whole-exome sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

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