25 MUTATIONS IN STXBP3 CONTRIBUTE TO VERY EARLY ONSET OF IBD, IMMUNODEFICIENCY AND HEARING LOSS

Very early-onset inflammatory bowel disease (VEO-IBD), defined by the onset of IBD before 6 years of age, is often associated with more severe and extensive disease than IBD in older patients. Some VEO-IBD cases have been linked to mutations in primary immunodeficiency genes, which regulate immunity and hyperinflammatory pathways, however the underlying pathophysiological mechanisms are still poorly understood. Here we describe eight patients from four unrelated families manifesting with VEO-IBD, immunodeficiency and severe bilateral sensorineural hearing loss - each carrying either heterozygous or compound heterozygous deleterious mutations in Syntaxin-Binding Protein 3 gene (STXBP3).