Novel NR4A1 Arg293Ser Mutation in Patients With Familial Crohn's Disease

The underlying etiology of Crohn's disease remains unknown. The aim of this study was to identify genomic alterations associated with the development of Crohn's disease in one Japanese family with a family history of Crohn's disease.

We performed whole-exome sequence and pedigree analysis of a Japanese family in which both sisters developed Crohn's disease. Whole-exome sequencing was performed using the Ion Torrent Proton™ system. Data from the Proton runs were initially processed using the Ion Torrent platform-specific pipeline software Ion Reporter. An autosomal dominant mode of inheritance was assumed, and stringent selection criteria were applied.

A substitution in the NR4A1 gene at codon 293 resulting in an amino acid change from arginine to serine was identified only in the affected sisters.

The impaired DNA-binding capacity of the NR4A1 protein due to an NR4A1 germline mutation may be a possible cause of Crohn's disease.