Panel-based genetic testing for inherited retinal disease screening 176 genes

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Inherited retinal diseases (IRD) are a group of genetic disorders affecting vision.
• Accurate genetic diagnosis is crucial for understanding IRD and guiding treatment.
• Next-generation sequencing (NGS) offers a comprehensive approach to genetic testing.

Purpose of the Study:

• To evaluate the diagnostic performance of a 176-retinal gene NGS panel (NGS 176) in patients with IRD.
• To determine the factors influencing the diagnostic yield of genetic testing for IRD.
• To assess the utility of NGS 176 as a first-tier genetic test for IRD.

Main Methods:

• A case series of 488 patients with IRD who underwent genetic testing between August 2016 and January 2018.
• Panel-based NGS testing (NGS 176) was performed, with targeted gene testing for specific suspected conditions.
• Variant pathogenicity prediction, evolutionary conservation analysis, and segregation studies were conducted for novel variants.

Main Results:

• A molecular diagnosis was achieved in 59.4% of patients.
• Younger patients, particularly children under 6 years old (92% diagnostic yield), were more likely to receive a diagnosis.
• A significant proportion of patients (8.4%) had their initial inheritance pattern revised post-testing.
• Specific IRD diagnoses, such as achromatopsia and congenital stationary night blindness, showed high diagnostic yields.

Conclusions:

• NGS 176 is a valuable and effective first-tier genetic test for a majority of IRD patients.
• Patient age and initial clinical diagnosis are key factors strongly associated with the success of genetic testing for IRD.
• The study supports the widespread adoption of NGS 176 for IRD diagnosis.