Effective smMIPs-Based Sequencing of Maculopathy-Associated Genes in Stargardt Disease Cases and Allied Maculopathies from the UK

Abstract

Macular dystrophies are a group of individually rare but collectively common inherited retinal dystrophies characterised by central vision loss and loss of visual acuity. Single molecule Molecular Inversion Probes (smMIPs) have proved effective in identifying genetic variants causing macular dystrophy. Here, a previously established smMIPs panel tailored for genes associated with macular diseases has been used to examine 57 UK macular dystrophy cases, achieving a high solve rate of 63.2% (36/57). Among 27 bi-allelic STGD1 cases, only three novel ABCA4 variants were identified, illustrating that the majority of ABCA4 variants in Caucasian STGD1 cases are currently known. We examined cases with ABCA4-associated disease in detail, comparing our results with a previously reported variant grading system, and found this model to be accurate and clinically useful. In this study, we showed that ABCA4-associated disease could be distinguished from other forms of macular dystrophy based on clinical evaluation in the majority of cases (34/36)

How to Set Up Genetic Counselling for Inherited Macular Dystrophies: Focus on Genetic Characterization

“…McClinton et al recently described a strategy using single-molecule molecular inversion probe (smMIP)-based sequencing; this strategy provides a coverage of 97.4% of the ABCA4 gene [55]. Despite the significant advantage of massive parallel sequencing, the main issue related to these new techniques is the consistent number of resulting information that requires a complex bioinformatic interpretation process and carries levels of uncertain significance [7].…”