The utility of genomic testing in the ophthalmology clinic: A review

Abstract

Genomic testing assesses many genes in one test. It is often used in the diagnosis of heterogeneous single gene disorders where pathogenic variation in one of many genes are known to cause similar phenotypes, or where a clinical diagnosis is difficult to reach. In the ophthalmic setting, genomic testing can be used to diagnose several groups of diseases, including inherited retinal dystrophies, paediatric cataract, glaucoma and anterior segment dysgenesis and other syndromic developmental disorders with eye involvement. The testing can encompass several modalities ranging from whole genome sequencing to exome sequencing or targeted gene panels. The advantages to the patient of receiving a molecular diagnosis include an end to the diagnostic odyssey, determination of prognosis and clarification of treatment, access to accurate genetic counselling, and confirming eligibility for clinical trials or genetic specific therapies. Genomic testing is a powerful addition to the diagnosis and management of inherited eye disease.

Multifaceted and Age-Dependent Phenotypes Associated With Biallelic PNPLA6 Gene Variants: Eight Novel Cases and Review of the Literature

“…For example, early-onset cases are often evaluated by ophthalmologists and initially screened for genes associated with visual impairment. Juvenile- and adult-onset cases are likely to be evaluated by different physicians depending on the specific presenting symptom ( 29 – 31 ). We suggest that PNPLA6 gene screening should also be considered in the diagnostic workout of patients with late-onset cerebellar signs, including patients presenting a CANVAS-like phenotype, when pathological expansions in the RFC1 gene are not detected.…”

The Role of the Ophthalmic Genetics Multidisciplinary Team in the Management of Inherited Retinal Degenerations—A Case-Based Review

“…In addition the variable visual impacts of IRDs, many patients also have retinal degeneration as part of a syndromic condition with multi-system involvement (e.g., deafness in Usher syndrome or neurological manifestations in spinocerebellar ataxia) [4]. The now well documented burden of disease highlights the importance of appropriate personalized management, care, and research into treatments for these patients [5][6][7][8][9][10].…”

“…Both clinical (e.g., multimodal imaging) and genetic diagnostic capacity is ever growing. The cost of genomic sequencing has dropped significantly over the past decade, allowing greater testing capacity, and has contributed to the growing utilisation of whole exome sequencing (WES) and whole genome sequencing (WGS), versus more limited panel-based testing [7,13]. However, the coordination and interpretation of these data is best served in a setting where genetic and clinical data is rationalized together.…”

Commentary: Genomic testing is a powerful tool in diagnosing and managing anterior segment dysgenesis

“…Genomic testing is a powerful addition to diagnosing and managing inherited eye disease. [ 2 3 4 5 ]…”

“…Genomic methods, such as genome-wide association studies, are potentially an effective tool to understand anterior segment dysgenesis and the individual’s susceptibility to the development of ASD. [ 2 3 4 5 6 ]…”