Case Report: A Novel Compound Heterozygous Mutation in IL-10RA in a Chinese Child With Very Early-Onset Inflammatory Bowel Disease

Abstract

Very early-onset inflammatory bowel disease (VEO-IBD) is defined as IBD diagnosed in children younger than 6 years of age. VEO-IBD is often associated with a monogenic etiology or primary immune deficiency. Here, we report the case of a 7-month-old Chinese girl diagnosed with VEO-IBD who had a variant in the interleukin-10 receptor A (IL-10-RA) gene. The patient presented with recurrent fevers, abdominal pain, diarrhea, perianal abscesses, and oral ulcers. Whole-exome sequencing (WES) identified a novel compound heterozygote mutation, c.395T>G (p.Leu132Arg)/ex.1del (p.?), in the IL-10RA gene of the patient. The missense mutation c.395T>G (p.Leu132Arg) was inherited from her mother, and ex.1del (p.?) was inherited from her father. Neither mutation has been reported previously. The IL-10RA function of the patient was defective, as demonstrated by a failure of signal transducer and activator of transcription 3 (STAT3) activation in peripheral blood mononuclear cells (PBMCs) stimulated with recombinant IL-10. The patient underwent matched unrelated peripheral blood hematopoietic stem cell transplantation (HSCT), and the clinical manifestations were dramatically improved. In summary, we identified a novel compound heterozygote mutation, c.395T>G (p.Leu132Arg)/ex.1del (p.?), in IL-10RA that caused VEO-IBD in a Chinese child, which further expands the mutational spectrum of IL-10RA.

Neonatal Crohn’s Disease Caused by Compound Homozygous Mutation in IL-10RA: A Case Report

“…Signal Transducer and Activator of Transcription 3 (STAT3) is phosphorylated as a result of this complex's activation of Janus Kinase-1 (JAK1) and Tyrosine Kinase-2 (TYR2). This promotes the production of downstream anti-inflammatory genes and has an anti-inflammatory effect [2,3,6,9]. According to recent research, 10% of VEO-IBD cases are caused by mutations in the IL-10RA gene, which mainly manifest as severe gastrointestinal symptoms in young children [1][2][3].…”

“…Five examples of intestinal malrotation in adults with concomitant Crohn's disease and midgut malrotation were reviewed and reported by Silverman J [8]. More research is required to determine whether there is a connection between these two conditions in pediatrics and if there is a genetic relationship that is responsible for their occurrence [9][10][11].…”

“…Crohn's Disease (CD) is an Inflammatory Bowel Disease (IBD) subtype; it is a chronic idiopathic transmural inflammatory condition that may involve the entire gastrointestinal tract with an unclear cause [1][2][3][4]. Patients younger than 2 years old account for 1% of all IBD, with an increasing incidence readily occurring [5][6][7][8][9][10][11]. Compared to adults and adolescents with lateonset IBD, children with VEO-IBD had more severe gastrointestinal symptoms, including significant colonic involvement, severe colitis with hematochezia, perianal abscess and fistulae.…”

“…Many monogenic defects have been found in VEO-IBD patients in the last few decades. Early detection is crucial since a delay in diagnosis and treatment might result in failure to thrive [9].…”

“…Here, we present the case of a 5month-old Palestinian baby with homozygous IL-10RA mutation-related VEO-IBD. The study reported the patient's clinical characteristics and genetic variations and whole-exome sequencing of blood samples was used to identify the IL-10RA's loss of function [9,12].…”