ABCA4 midigenes reveal the full splice spectrum of all reported noncanonical splice site variants in Stargardt disease

Posted on: Tuesday 5 December 2017

Based on the work of Riccardo Sangermano, Mubeen Khan, Stephanie Cornelis, PhD candidates in the group of prof. Frans Cremers in the Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands, a new approach was recently published in the renown journal Genome Research which enables the systematic and quick testing of putative causal sequence variants for their effect on RNA splicing and thereby on the protein.

This new procedure was established for the 130-kb large ABCA4 gene that is implicated in Stargardt disease, the most frequent juvenile macular dystrophy. In this paper, all 44 published and three novel noncanonical splice site variants were tested which allowed an accurate classification of the effect of these variants, ranging from benign to severe. These studies were sponsored by RP Fighting Blindness (UK), Foundation Fighting Blindness (USA) and the European Union.

“This is exciting news and proves once again that collaborative funding of projects is key to the continued development of future treatments,” commented Tina Houlihan, Chief Executive at RP Fighting Blindness. “We’re delighted with these results, and that more efficient testing is now possible for this significant condition. We look forward to seeing further advances in the coming years, and we are working hard to raise the profile of eye research in the UK and beyond.”