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Review
. 2021 Dec 14;16(1):514.
doi: 10.1186/s13023-021-02145-0.

Genetic testing and diagnosis of inherited retinal diseases

Byron L Lam  1 , Bart P Leroy  2   3 , Graeme Black  4   5   6 , Tuyen Ong  7 , Dan Yoon  8 , Karmen Trzupek  9
Affiliations
Review

Genetic testing and diagnosis of inherited retinal diseases

Byron L Lam et al. Orphanet J Rare Dis. .

Abstract

Inherited retinal diseases (IRDs) are a diverse group of degenerative diseases of the retina that can lead to significant reduction in vision and blindness. Because of the considerable phenotypic overlap among IRDs, genetic testing is a critical step in obtaining a definitive diagnosis for affected individuals and enabling access to emerging gene therapy-based treatments and ongoing clinical studies. While advances in molecular diagnostic technologies have significantly improved the understanding of IRDs and identification of disease-causing variants, training in genetic diagnostics among ophthalmologists is limited. In this review, we will provide ophthalmologists with an overview of genetic testing for IRDs, including the types of available testing, variant interpretation, and genetic counseling. Additionally, we will discuss the clinical applications of genetic testing in the molecular diagnosis of IRDs through case studies.

Keywords: Case studies; Genetic counseling; Genetic testing; Inherited retinal disease; Molecular diagnosis; Next-generation sequencing; Ophthalmology.

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Conflict of interest statement

BLL has received research and clinical trial funding from the National Eye Institute, AGTC, Biogen, Editas Medicine, Pixium Vision, and ProQR and consultancy fees from Biogen and ProQR. BPL has received consultancy fees from Bayer, GenSight Therapeutics, IVERIC Bio, Novartis Pharma International & Belgium, Spark Therapeutics, ProQR Therapeutics, REGENXBIO, and Vedere Bio; has received travel support from GenSight Therapeutics, IVERIC Bio, Novartis Pharma International & Belgium, Spark Therapeutics, and ProQR Therapeutics; and reports an unpaid consultancy with LookoutGTx. GB has received consultancy fees from GenSight Therapeutics and Novartis Pharma International. TO has nothing to disclose. DY is an employee and stockholder of Biogen. KT has received an honorarium from Biogen for speaking at an internal training event.

Figures

Fig. 1
Fig. 1
Fundoscopic images from a 60-year-old healthy male with a clinical diagnosis of choroideremia. The genetic testing with next-generation sequencing panel showed the individual was negative for pathogenic mutations of the CHM gene and positive for 2 novel heterozygous mutations of the C2orf71 gene
Fig. 2
Fig. 2
Funduscopic images from 7-year-old boy with a clinical diagnosis of RPGR-mutated X-linked retinitis pigmentosa
Fig. 3
Fig. 3
Decision tree for case scenarios. IRD, inherited retinal disease
See this image and copyright information in PMC

References

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