Exome Sequencing
We performed exome sequencing in all probands in whom no mutation had been identified by targeted gene analyses and in parental samples where available. We performed exome sequencing using the Nextera Rapid Capture Exome Kit (Illumina). We prepared libraries from 50 ng genomic DNA using the Nextera DNA Sample Preparation Kit (Illumina). On average 33M reads mapped to the pulldown and 86% of targeted bases had ≥15× coverage. The captured libraries were PCR amplified using the supplied paired-end PCR primers. Exome sequencing in 57 samples was performed before the Nextera Exome Kit was available using the TruSeq Exome Enrichment Kit, which includes the 14 genes involved in OGID. When converting our exome pipeline from TruSeq to Nextera, we undertook in-house evaluation and validation to ensure that the performance was equivalent. Sequencing was performed on an llumina HiSeq 2000 or HiSeq 2500 (high output mode) using v3 chemistry and generating 2 × 101 bp reads.