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

Based on the work of Riccardo Sangermano, Mubeen Khan, Stephanie Cornelis, PhD candidates in the group of Professor Frans Cremers in the Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands, a new approach was recently published in the renowned 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.

*Sangermano R, *Khan M, Cornelis SS, Richelle V, Albert S, Elmelik D, Garanto A, Qamar R, Lugtenberg D, van den Born LI, Collin RWJ, Cremers FPM. *Equal contributions.

Genome Res. 2017 Nov 21. pii: gr.226621.117. doi: 10.1101/gr.226621.117. [Epub ahead of print]