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.


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


  • 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.).