WGS was performed on samples from study participants as part of the NIHR BioResource Rare Diseases study.5 Blood DNA samples were fragmented (mean size 450 bp) with the Covaris LE220 kit and further processed with an Illumina TruSeq DNA PCR-Free Library Prep Kit. Libraries were sequenced with an Illumina HiSeq 2500 sequencer with one library per two lanes. FASTQ files were generated by HiSeq Analysis Software v.2.0 (Illumina). Alignment (GRCh37) and variant calling (including structural variants [SVs])9, 10 was performed with Isaac (Illumina).