Exploring genotype–phenotype correlations in three pediatric patients with IL10RA variants and very early-onset inflammatory bowel disease

Abstract Background Very early onset inflammatory bowel disease (VEO-IBD) is a severe chronic intestinal inflammatory disorder with onset in infancy. Mutations in the interleukin-10 (IL-10) receptor A (IL10RA) gene represent a key pathogenic mechanism of VEO-IBD; however, the genotype–phenotype correlations remain unclear. Objective This study aims to describe and compare the clinical features, genotypes, and family segregation data of three pediatric patients with IL10RA mutation-associated VEO-IBD to explore potential associations between different IL10RA mutation sites and types (compound heterozygous or homozygous) and clinical phenotypes. Methods Three VEO-IBD patients harboring IL10RA mutations diagnosed at our hospital from July 2022 to December 2024 were retrospectively enrolled. Genetic testing and family segregation analysis were performed for all patients. Detailed clinical data, including age of onset, manifestations, examinations, and treatment were collected. Phenotypic features were summarized and compared among different mutation types to establish genotype–phenotype relationships. Results All patients developed symptoms within six months, mainly diarrhea, perianal abscesses, and fistulas. Patient 1 had a homozygous c.301 C > T(p.Arg101Trp) mutation with severe perianal disease. Patient 2 carried compound heterozygous c.301 C > T(p.Arg101Trp) and c.537G > A(p.Thr179Thr) mutations, exhibiting recurrent oral ulcers, perianal lesions, and growth retardation, exhibiting a severe phenotype linked to compound/homozygous mutations. Patient 3 had a novel compound heterozygous IL10RA c.421G > A(p.Gly141Arg) mutation along with (c.301 C > T(p.Arg101Trp), with milder symptoms with a perianal disease and growth delay. Conclusion Our study identified homozygous or compound heterozygous IL10RA mutations associated with the VEO-IBD phenotype, with severe clinical features. The newly discovered c.421G > A(p.Gly141Arg) mutation may broadens the genetic spectrum associated with the disease.Although small in scale, this case series provides a meaningful contribution to the growing body of evidence on VEO-IBD.