One of the most striking results of this study is the high diagnostic yield of genetic testing in OGID; a genetic cause was identified in 50% (357/710) of case subjects. This is likely to be an underestimate as we have been conservative in attributing pathogenicity to OGID gene variants and additional OGID genes almost certainly exist. Indeed, among the 132 trios in whom a definitive cause was not found, a de novo mutation possibly associated with their phenotype was present in 28; for example, two had de novo nonsynonymous variants in XRN1.