The landscape of submicroscopic structural variants at the OPN1LW/OPN1MW gene cluster on Xq28 underlying blue cone monochromacy

Significance Blue cone monochromacy (BCM) is an inherited retinal disorder characterized by low vision and poor color vision and caused by mutations in the multicopy gene cluster encoding the long- and middle-wavelength-sensitive cone photoreceptor visual pigments. We showed that structural genomic mutations at the gene cluster explain about one-third of those affected among 213 genetically confirmed BCM families. Our study expands the known spectrum of structural mutations causing BCM by a factor of 4 and provides a comprehensive landscape of their extent and fine structure as well as a deep insight into the underlying molecular mechanisms. We observed evidence that occurrence of BCM-linked structural mutations may be driven by inherent increased instability of individual gene clusters with large copy numbers.

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