Practical guide to genetic screening for inherited eye diseases

Abstract

Genetic eye diseases affect around one in 1000 people worldwide for which the molecular aetiology remains unknown in the majority. The identification of disease-causing gene variant(s) allows a better understanding of the disorder and its inheritance. There is now an approved retinal gene therapy for autosomal recessive RPE65-retinopathy, and numerous ocular gene/mutation-targeted clinical trials underway, highlighting the importance of establishing a genetic diagnosis so patients can fully access the latest research developments and treatment options. In this review, we will provide a practical guide to managing patients with these conditions including an overview of inheritance patterns, required pre- and post-test genetic counselling, different types of cytogenetic and genetic testing available, with a focus on next generation sequencing using targeted gene panels, whole exome and genome sequencing. We will expand on the pros and cons of each modality, variant interpretation and options for family planning for the patient and their family. With the advent of genomic medicine, genetic screening will soon become mainstream within all ophthalmology subspecialties for prevention of disease and provision of precision therapeutics.

Development the Algorithm for Virtual Screening of Protein Polymorphisms Affecting Their Structural and Functional Properties

“…During the development of the algorithm, there were technical difficulties associated with the structure of the SNP database page, but this problem can be eliminated by using additional libraries and scripts. The algorithm can be modified by adding various elements for the accuracy of the search, which can complement existing methods for diagnosing and detecting genetic diseases (Méjécase et al, 2020).…”

The Impact of Modern Technologies on Molecular Diagnostic Success Rates, with a Focus on Inherited Retinal Dystrophy and Hearing Loss

“…Therefore, a shift from exome to genome sequencing will be observed in clinical diagnostics in the near future to overcome the diagnostic gap observed in the application of WES. In 2020, Méjécase et al provided a practical and cost-effective guideline for current and future genetic testing of RDs, in which they proposed to utilize WES or targeted NGS for the initial screening of exons and flanking intronic regions of (candidate or known RD) genes, reserving WGS solely for cases that remained unresolved [ 63 ].…”

Cloud-based genomics pipelines for ophthalmology: reviewed from research to clinical practice

“…54 The current workflow in clinical genomics is summarized in Figure 1; currently, results are obtained in 2-6 months or longer depending on individual circumstances. 32 The clinical utility of genetic screening for inherited retinal diseases includes potential gene-therapy treatment, genetic counselling, and eligibility for clinical trials. 55…”

“…31 As a result, genetic testing is becoming an increasingly popular investigation in ophthalmology. 32 The examples described so far often rely on targeted genetic testing, which usually only tests specific regions of DNA for a specific type of variation. The data produced is thus of limited use beyond the specific condition tested and does not enable future discovery of other types of variation beyond the examined region.…”