Genetic Variants and Impact in PDE6B Rod-Cone Dystrophy

Abstract

Phosphodiesterase 6B (PDE6B) is one of the most commonly mutated genes to cause autosomal recessive retinitis pigmentosa (RP), also known as rod-cone dystrophy. The PDE6B protein plays a crucial role in the phototransduction cascade. With the emerging possibility of genetic therapy for autosomal recessive PDE6B-related retinitis pigmentosa, knowledge regarding the pathogenicity and functional significance of identified PDE6B variants is crucial for genetic information for families and access to clinical trials. We collected all PDE6B variants reported in 207 autosomal recessive RP patients in publications before June 2019. The 101 unique variants obtained were classified according to the American College of Medical Genetics and Genomics guidelines. Our study provides information on the variant type, location, and predicted pathogenicity of the variants. It also highlights the need for ongoing review, as well as additional data from functional assays, to better understand the clinical significance of PDE6B variants.