The Oculome: a genetic test to diagnose a diverse range of ocular birth anomalies

Abstract

Purpose : Each year up to 4 in 10,000 children in the UK are diagnosed as severely sight impaired. More than 25% of cases may be inherited, with the majority remaining undiagnosed due to the large number of genes underlying these highly heterogeneous conditions. We developed a new next generation sequencing (NGS) panel test, the Oculome, which enables genetic diagnosis in a diverse range of ocular birth defects and inherited eye conditions, including syndromic, metabolic, developmental, or sensory abnormalities.

Methods : A custom-designed Agilent SureSelect QXT target capture method was used to capture 436 genes representing known eye disease genes. Panel development included sequencing n=288 clinical samples using Illumina HiSeq2500 with 125 bp paired end sequencing reads. We achieved >30 X read-depth for 99.5% of the targeted region. Bioinformatics analysis was performed using an in-house pipeline and annotated using Variant Effect Predictor v73.

Results : The Oculome panel covers 436 genes subdivided into 5 overlapping sub-panels for retinal dystrophies (212), anterior segment dysgenesis and glaucoma (47), microphthalmia-anophthalmia-coloboma (MAC) (86), congenital cataracts and lens-associated (84) and albinism (16). Analysis of n=160 paediatric samples resulted in a definitive diagnosis in n=41 (25.6%) with variability in diagnostic yield between phenotypic sub-panels e.g. retinal dystrophies (57.6% cases solved) and anterior segment/glaucoma (26.8% cases solved).

Conclusions : The Oculome enabled the molecular diagnosis of a significant number of cases in our sample cohort of varied congenital ocular conditions. The Oculome test is available at the Great Ormond Street North East Thames NHS Regional Genetics Service Laboratories, London UK. [email protected]

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.