Mutations in the cone opsin gene cluster underlying Blue ConeMonochromatism and X-linked cone dystrophy: implementation oftargeted nanopore long read sequencing and investigating thediversity of the c.607T>C/p.(Cys203Arg) variant-bearing gene clusters

02.12.2024 bis 30.11.2027

Mutations in the OPN1LW/OPN1MW gene cluster which encodes the photopigments of the long wavelength-sensitive (red) and middle wavelength-sensitive (green) cone photoreceptors in the human retina cause Blue Cone Monochromacy (BCM) and other rare X-linked inherited forms of cone dysfunction disorders associated with low
vision, colour vision deficiency and photoaversion. In this project - in continuation of prior work and funding of this research topic - we will further improve and implement targeted long read nanopore sequencing to investigate unresolved structural mutations and the order of gene copies in patients with complex OPN1LW/OPN1MW
gene clusters thereby closing a current analytical gap in genetic testing of such patients. Moreover, we will investigate the astonishing structural diversity of gene clusters harboring a specific point mutation (c.607T>C;p.(Cys203Arg)) which account for 45% of BCM cases in our patient cohort. These investigations may enable testing of competitive hypothesis on the molecular mechanisms underlying the heterogeneity in the structure and composition and the dynamics of such rearrangements at the OPN1LW/OPN1MW gene cluster.