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Diagnostic yield of candidate genes in an Australian corneal dystrophy cohort


Souzeau, E and Siggs, OM and Mullany, S and Schmidt, JM and Hassall, MM and Dubowsky, A and Chappell, A and Breen, J and Bea, H and Nicholl, J and Hadler, J and Kearns, LS and Staffieri, SE and Hewitt, AW and Mackey, DA and Gupta, A and Burdon, KP and Klebe, S and Craig, JE and Mills, RA, Diagnostic yield of candidate genes in an Australian corneal dystrophy cohort, Molecular genetics and genomic medicine, 10, (10) Article e2023. ISSN 2324-9269 (2022) [Refereed Article]

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2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution-Non Commercial-No Derivs License. Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1002/mgg3.2023


Corneal dystrophies describe a clinically and genetically heterogeneous group of inherited disorders. The International Classification of Corneal Dystrophies (IC3D) lists 22 types of corneal dystrophy, 17 of which have been demonstrated to result from pathogenic variants in 19 identified genes. In this study, we investigated the diagnostic yield of genetic testing in a well-characterised cohort of 58 individuals from 44 families with different types of corneal dystrophy. Individuals diagnosed solely with Fuchs endothelial corneal dystrophy were excluded. Clinical details were obtained from the treating ophthalmologist. Participants and their family members were tested using a gene candidate and exome sequencing approach. We identified a likely molecular diagnosis in 70.5% families (31/44). The detection rate was significantly higher among probands with a family history of corneal dystrophy (15/16, 93.8%) than those without (16/28, 57.1%, p = .015), and among those who had undergone corneal graft surgery (9/9, 100.0%) compared to those who had not (22/35, 62.9%, p = .041). We identified eight novel variants in five genes and identified five families with syndromes associated with corneal dystrophies. Our findings highlight the genetic heterogeneity of corneal dystrophies and the clinical utility of genetic testing in reaching an accurate clinical diagnosis.

Item Details

Item Type:Refereed Article
Keywords:Genetics, eye disease, inherited
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:153570
Year Published:2022
Funding Support:National Health and Medical Research Council (1059954)
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-09-26
Last Modified:2022-11-30
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