We investigate the mechanism of GLA pseudoexon activation in Fabry disease.
The prevalent c.639 + 919 G > A mutation disrupts the binding of hnRNP A1/A2 to an ESS.
The GLA ESS is a general inhibitory motif able to inhibit also other pseudoexons.
HnRNP F/H are also involved in the regulation as enhancers of the pseudoexon.
SSOs might be a relevant therapy option as they restore normal GLA splicing.