Whole exome sequencing of patients who resolved Crohn\u2019s disease and complex regional pain syndrome following treatment for paratuberculosis

J Todd Kuenstner,Maher Kali,Christine Welch

doi:10.1186/s13099-019-0311-z

J Todd Kuenstner, Maher Kali + Show 1 more

Open Access

https://doi.org/10.1186/s13099-019-0311-z

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Abstract

BackgroundA 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.ResultsWe 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.ConclusionsThe 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.

Highlights

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)
We recruited members of a single family where individuals were affected by asthma, CD, hypothyroidism and CRPS and performed whole exome sequencing on 10 members of the family
We used the filter chains for models 1, 2 and 5 in Table 2. with the following modifications: (1) The minor allele frequency and Polyphen filters were removed, (2) Sequence ontology was expanded to include 5′ and 3′ UTRs, and (3) A filter that selected for variants present in DDX58, IL10, IL12B, MBL2, SLC11A1 and two Tuberculin Skin Test Reactivity loci (TST1 11p14-15, TST2, 5p15) was added [11,12,13,14]

Summary

Introduction

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 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. Over 140 genetic mutations have been identified in CD [5] These two areas of research are probably complementary because some of the genetic mutations, may indicate increased susceptibility to MAP infection. The NOD2 mutation found in some CD patients is associated with susceptibility to MAP infection in cattle [6]. Two of the cases (case 1 with CD and asthma and case 2 with CRPS, hypothyroidism and Raynaud’s phenomenon) were treated with a combination of anti-MAP antibiotics and ultraviolet blood irradiation (UVBI) with resolution of the diseases and inability to culture MAP in post

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