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

Benjamin Mc Clinton; Zelia Corradi; Martin McKibbin; Daan M Panneman; Susanne Roosing; Erica G M Boonen; Manir Ali; Christopher M Watson; David H Steel; Frans P M Cremers; Chris F Inglehearn; Rebekkah J Hitti-Malin; Carmel Toomes

doi:10.3390/genes14010191

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

Genes (Basel). 2023 Jan 11;14(1):191. doi: 10.3390/genes14010191.

Authors

Benjamin Mc Clinton¹, Zelia Corradi^{2

3}, Martin McKibbin^{1

4}, Daan M Panneman^{2

3}, Susanne Roosing^{2

3}, Erica G M Boonen^{2

3}, Manir Ali¹, Christopher M Watson^{1

5}, David H Steel^{6

7}, Frans P M Cremers^{2

3}, Chris F Inglehearn¹, Rebekkah J Hitti-Malin^{2

3}, Carmel Toomes¹

Affiliations

¹ Leeds Institute of Medical Research, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK.
² Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
³ Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
⁴ Department of Ophthalmology, St. James's University Hospital, Leeds LS9 7TF, UK.
⁵ North East and Yorkshire Genomic Laboratory Hub, Central Lab, St. James's University Hospital, Leeds LS9 7TF, UK.
⁶ Sunderland Eye Infirmary, Sunderland SR2 9HP, UK.
⁷ The Bioscience Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, 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).

Keywords: ABCA4; NGS; Stargardt; inherited retinal diseases; maculopathies; smMIPs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP-Binding Cassette Transporters / genetics
Alleles
Humans
Macular Degeneration* / genetics
Retinal Dystrophies* / genetics
Stargardt Disease / genetics
United Kingdom

Substances

ABCA4 protein, human
ATP-Binding Cassette Transporters

Grants and funding

This work was supported by a Horizon 2020, Marie Sklodowska-Curie Innovative Training Network entitled European Training Network to Diagnose, Understand and Treat Stargardt Disease, a Frequent Inherited Blinding Disorder-StarT (813490) (to C.T., C.I., F.P.M.C.), by Fighting Blindness Ireland and the HRCI HRB Joint Funding Scheme 2020-007, by Stichting Oogfonds Nederland (UZ 2020-17), Pro Retina Deutschland, Stichting tot Verbetering van het Lot der Blinden, Stichting voor Ooglijders and the Stichting Blindenhulp (to F.P.M.C.) and by EJPRD19-234 (Solve-RET) (to F.P.M.C. and S.R.).