Findings from a Genotyping Study of over 1000 People with Inherited Retinal Disorders in Ireland

• Main Authors: Laura Whelan, Adrian Dockery, Niamh Wynne, Julia Zhu, Kirk Stephenson, Giuliana Silvestri, Jacqueline Turner, James J. O’Byrne, Matthew Carrigan, Peter Humphries, David Keegan, Paul F. Kenna, G. Jane Farrar
• Format: Article
• Language: English
• Published: MDPI AG 2020-01-01
• Series: Genes
• Subjects: inherited eye disease; ophthalmic genetics; genomics; next generation sequencing; retinopathy; rare variants; novel variants
• Online Access: https://www.mdpi.com/2073-4425/11/1/105

The Irish national registry for inherited retinal degenerations (Target 5000) is a clinical and scientific program to identify individuals in Ireland with inherited retinal disorders and to attempt to ascertain the genetic cause underlying the disease pathology. Potential participants first undergo a clinical assessment, which includes clinical history and analysis with multimodal retinal imaging, electrophysiology, and visual field testing. If suitable for recruitment, a sample is taken and used for genetic analysis. Genetic analysis is conducted by use of a retinal gene panel target capture sequencing approach. With over 1000 participants from 710 pedigrees now screened, there is a positive candidate variant detection rate of approximately 70% (495/710). Where an autosomal recessive inheritance pattern is observed, an additional 9% (64/710) of probands have tested positive for a single candidate variant. Many novel variants have also been detected as part of this endeavor. The target capture approach is an economic and effective means of screening patients with inherited retinal disorders. Despite the advances in sequencing technology and the ever-decreasing associated processing costs, target capture remains an attractive option as the data produced is easily processed, analyzed, and stored compared to more comprehensive methods. However, with decreasing costs of whole genome and whole exome sequencing, the focus will likely move towards these methods for more comprehensive data generation.