Whole exome sequencing of patients who resolved Crohn’s disease and complex regional pain syndrome following treatment for paratuberculosis

Abstract

Abstract Background A whole exome sequencing study was performed on an extended family including a patient with Crohn’s disease (CD) and a patient with complex regional pain syndrome (CRPS). The patient with CD and the patient with CRPS have experienced resolution of their disease following treatment for paratuberculosis. The study was performed in order to determine if there is an unusual mutation in this extended family that would explain the susceptibility to mycobacterial infection among many of the members. Results We identified sets of rare single nucleotide polymorphisms (SNPs) that were shared among affected family members, including variants in two genes, IL15RA and CASP10, which have established roles in the immune response. In addition, the CD and CRPS patients were found to have heterozygous mutations in MBL2 and DDX58, mutations that have been associated with susceptibility to tuberculosis. Conclusions The IL15RA and CASP10 variants may contribute to the disease symptoms exhibited in this family. The finding of SNPs associated with immune function supports a complementary role of infection and genetics in these diseases.

Keywords

• Mycobacterium avium ssp. paratuberculosis
• Crohn’s disease
• Complex regional pain syndrome
• Lymphangiomatosis
• Type 1 diabetes mellitus
• Genetic susceptibility