Whole genome sequencing is enhancing the ability to identify disease causing mutations in inherited paediatric cataracts (PC), a heterogeneous rare disease that causes visual impairment. We are investigating unsolved families from Australia’s largest repository of PC DNA, which contains 191 families. Nine large families, with at least 3 affected individuals each, have been selected for linkage analysis. All available DNA samples (n=96) have undergone genome-wide genotyping using Illumina OmniExpress SNP arrays. Parametric linkage analysis, using Merlin, is being performed with a relevant disease model for each family. Whole genome sequencing of an affected individual from each family was performed on an Illumina X10 platform. The Churchill pipeline was used to align fastq files to hg19, and variant calling was performed using SAMtools for SNPs and Platypus for indels. Structural variants will also be considered. Variants within putative linkage regions are filtered for frequency (MAF <0.01) and predicted functionality (using tools such as CADD). Using this pipeline, the PC in family CRVEEH66 have been linked to a 6.8Mb region at Xq24 (LOD=2.53) and two additional regions at 1q42.2-1q43 and 3q26.31-3q26.32 (LOD=2.44). A Complete Genomics™ whole genome sequence of the proband enabled the identification of a 127kb deletion that truncates the PGRMC1 gene following exon 1 and completely removes a long non-coding RNA gene LOC101928336, located in the chromosome Xq24 region. This variant was not detectable by prior exome or Sanger sequencing and these are novel PC candidate genes. This highlights the utility of whole genome sequencing for identifying putative disease causing structural and non-coding variants, which have not been explored in PC. This work will provide these Australian families with a molecular diagnosis and enable genetic screening. The discovery of novel genes will expand the suite of genes available for screening in other patients and improve our understanding of cataract pathogenesis.