Journal article

Revealing hidden genetic diagnoses in the ocular anterior segment disorders

Alan Ma, Saira Yousoof, John R Grigg, Maree Flaherty, Andre E Minoche, Mark J Cowley, Benjamin M Nash, Gladys Ho, Thet Gayagay, Tiffany Lai, Elizabeth Farnsworth, Emma L Hackett, Katrina Fisk, Karen Wong, Katherine J Holman, Gemma Jenkins, Anson Cheng, Frank Martin, Tanya Karaconji, James E Elder Show all

Genetics in Medicine | NATURE PUBLISHING GROUP | Published : 2020


PURPOSE: Ocular anterior segment disorders (ASDs) are clinically and genetically heterogeneous, and genetic diagnosis often remains elusive. In this study, we demonstrate the value of a combined analysis protocol using phenotypic, genomic, and pedigree structure data to achieve a genetic conclusion. METHODS: We utilized a combination of chromosome microarray, exome sequencing, and genome sequencing with structural variant and trio analysis to investigate a cohort of 41 predominantly sporadic cases. RESULTS: We identified likely causative variants in 54% (22/41) of cases, including 51% (19/37) of sporadic cases and 75% (3/4) of cases initially referred as familial ASD. Two-thirds of sporadic ..

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Awarded by National Health and Medical Research Council (NHMRC)

Funding Acknowledgements

R.V.J. and J.R.G. acknowledge support from National Health and Medical Research Council (NHMRC) grant APP1116360, the NSW Office of Health and Medical Research, Costco, the Sydney Research Excellence Initiative, and the Ophthalmic Research Institute of Australia. We thank the Kinghorn Centre for Clinical Genomics for assistance with production and processing of genome sequencing data. M.J.C. was supported by a NSW Health Early-Mid Career Fellowship. We thank the families involved in this study and supporting clinicians and laboratory staff for their time and efforts.