A Genome Sequencing Program for Novel Undiagnosed Diseases

PURPOSE: The Scripps Idiopathic Diseases of huMan (IDIOM) study aims to discover novel gene-disease relationships and provide molecular genetic diagnosis and treatment guidance for individuals with novel diseases using genome sequencing integrated with clinical assessment and multidisciplinary case review. METHODS: Here we describe the IDIOM study operational protocol and initial results. RESULTS: 121 cases underwent first tier review by the principal investigators to determine if the primary inclusion criteria were satisfied, 59 (48.8%) underwent second tier review by our clinician-scientist review panel, and 17 (14.0%) patients and their family members were enrolled. 60% of cases resulted in a plausible molecular diagnosis. 18% of cases resulted in a confirmed molecular diagnosis. 2 of 3 confirmed cases led to the identification of novel gene-disease relationships. In the third confirmed case, a previously described but unrecognized disease was revealed. In all three confirmed cases, a new clinical management strategy was initiated based on the genetic findings. CONCLUSIONS: Genome sequencing provides tangible clinical benefit for individuals with idiopathic genetic disease, not only in the context of molecular genetic diagnosis of known rare conditions, but also in cases where prior clinical information regarding a new genetic disorder is lacking.