Characterization of novel and large fragment deletions in exon 1 of the IL10RA gene in Chinese children with very early onset inflammatory bowel diseases

BACKGROUND: Defects in interleukin 10 (IL10) and its receptors are particularly involved in very early onset inflammatory bowel disease (VEOIBD). However, large fragment deletions of IL10 receptor A (IL10RA) are rare. METHODS: VEOIBD patients with confirmed mutations in the IL10RA gene were enrolled from January 1, 2019 to June 30, 2020. The clinical features and endoscopic-radiological findings of the patients with large fragment deletions of the IL10RA gene were determined and followed up. RESULTS: Thirty-five patients with IL10RA gene mutations, namely, 28 compound heterozygous mutations and 7 homozygote mutations, were enrolled in this study. Six patients carried the reported point mutation c.301C > T (p. R101RW) or c.537 G > A (p. T179T) in one locus and a large fragment deletion in exon 1 in another locus, which were novel mutations in this gene. A 333-bp deletion of exon 1 (117857034–11857366 del) was the main mutation in this locus in 85.7% of the patients with large fragment deletions. The time of disease onset ranged from birth to 4 years, and diarrhea was the main initial symptom. In total, 6/7 patients had perianal complications, including perianal abscess, fistula and skin tags. Six patients accepted thalidomide treatment, 5/7 accepted mesalamine, 3/7 accepted hematopoietic stem cell transplantation (HSCT), and 3/7 were waiting for HSCT. CONCLUSIONS: We identified a novel large deletion of exon 1 involving the IL10RA gene for the first time and showed the characteristics of VEOIBD patients. This study expands the spectrum of Chinese VEOIBD patients with IL0RA gene mutations.