Humanexome 12 v1 csnp array

Clinical WES testing was conducted as previously described for the Baylor WES cohort^{27 (link)}. Briefly, extracted DNA was subjected to an in-house exome capture platform (VCRome version 2.1) and sequenced using either an Illumina Genome Analyzer IIx platform or the Illumina HiSeq 2000 platform. Samples were additionally analyzed by an Illumina HumanExome-12 v1 cSNP array for quality-control assessment of exome data, as well as for detecting large copy-number variants and regions of absence of heterozygosity. Iranian clinical WES testing utilized commercial platforms (Beijing Genomic Institute, Shenzhen, China; Macrogen, Seoul, South Korea)^{30 (link)}. WES performed on DNA from the proband of the first family; the second family (Family 2) had WES performed on parents due to unavailability of samples from deceased children. Haplotype analysis was performed as previously described^{31 (link)}. Presence or absence of putatively pathogenic variants were compared against the 1000 Genomes Project^{32 (link)}, NHLBI GO Exome Sequencing Project, gnomAD, as well as the ethnically-matched GME Variome and Iranome. Confirmation of the WES-identified JPH2-p.E641* variant was conducted in the probands of each kindred using direct Sanger sequencing. Further, variant positivity was evaluated in all kindred using Sanger sequencing.