Dr. Miriam Bauwens

Deciphering the pathogenic effect of missense variants of uncertain significance in RPE65, a target for gene therapy
(promotor of the grant: Prof. Elfride De Baere)

Biallelic mutations in the RPE65 enzyme can give rise to early-onset congenital blindness.

Ghent University Hospital is pioneering in treating patients with proven RPE65-associated IRD with Luxturna gene therapy.To be eligible for this treatment, an unequivocal molecular diagnosis of

IRD with biallelic pathogenic RPE65 variants is imperative. Over 100 pathogenic variants in

RPE65 have been reported. However, in the RPE65 variant database 33 unique variants of unknown significance (VUS) are listed, causing uncertainty about molecular diagnoses in patients with IRD. Biochemical assays have been developed for the functional assessment of RPE65 variants, allowing to measure residual isomerase activity of RPE65. Only a limited number of RPE65 variants have been tested however due to the low throughput of the assays.

In this project Miriam will develop an advanced workflow for in vitro enzymatic assessment of RPE65 VUS to increase the number of certain molecular diagnoses in LCA2 and RPE65-associated IRD.