Compound heterozygous mutations in IL10RA combined with a complement factor properdin mutation in infantile-onset inflammatory bowel disease

Objectives Inflammatory bowel diseases (IBDs) are chronic and multifactorial diseases resulting from a complex interaction of host genetic factors and environmental stimuli. Although many genome-wide association studies have identified host genetic factors associated with IBD, rare Mendelian forms of IBD have been reported in patients with very early onset forms. Therefore, this study aimed to identify genetic variants associated with infantile-onset IBD. Participants and methods We obtained genomic DNA from whole blood samples of a male patient with infantile-onset IBD and nonconsanguineous Korean parents. Whole-exome sequencing was performed using trio samples. Then, we analyzed the data using susceptibility genes for monogenic forms of IBD and various immunodeficiencies and protein structural analysis. Results The patient who presented with oral aphthous ulcers at the age of 14 days suffered from severe colitis and was refractory to medical treatment. Compound heterozygous mutations in IL10RA (p.R101W; p.T179T) were found in the patient. In addition, a hemizygous mutation in complement factor properdin (CFP) (p.L456V) located on the X-chromosome was detected, inherited from the patient's mother. Protein structural modeling suggested impaired properdin subunit interactions by p.L456V that may hamper protein oligomerization required for complement activation. Conclusion This study identified compound heterozygous mutations in IL10RA combined with a hemizygous CFP mutation in infantile-onset IBD by using whole-exome sequencing. CFP p.L456V may exacerbate symptoms of infantile-onset IBD by disturbing oligomerization of properdin.