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Case Reports
. 2021 May 25:9:678390.
doi: 10.3389/fped.2021.678390. eCollection 2021.

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

Fang Dong  1 , Fangfei Xiao  1 , Ting Ge  1 , Xiaolu Li  1 , Wuhen Xu  2 , Shengnan Wu  2 , Ting Zhang  1   3 , Yizhong Wang  1   3
Affiliations
Case Reports

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

Fang Dong et al. Front Pediatr. .

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.

Keywords: IL10RA; STAT3 phosphorylation analysis; VEO-IBD; compound heterozygote mutation; whole-exome sequencing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Confirmation of novel IL-10RA variants. (A) c.395T>G variant (red arrow) confirmed by Sanger sequencing. (B) Validation of the ex.1del (p.?) variant by quantitative PCR. Genomic DNA was extracted from peripheral blood from the patient, her parents and healthy controls. Reactions were set up using one set of primers upstream and downstream of exon 1 in triplicate. The β-actin gene served as a reference gene. The 2−ΔΔCT method was used to calculate the copy number. Samples with normalized ratios (NRs) <0.1 denote individuals with homozygous deletion, samples with NRs of about 0.5 denote individuals with heterozygous deletion, sample with NRs of ~1 denote healthy individuals (two copies), and samples with NRs of ~1.5 or more denote individuals with copy number gain.
Figure 2
Figure 2
Western blot showing the patient had normal expression of p-STAT3 in peripheral blood mononuclear cells (PBMCs) in response to IL-6 (positive control) stimulation but showed defective STAT3 phosphorylation under IL-10 stimulation. −, untreated; +, treated.
See this image and copyright information in PMC

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