Cone opsins, colour blindness and cone dystrophy: Genotype-phenotype correlations

J C Gardner, M Michaelides, A J Hardcastle
2016 South African Medical Journal  
My interest in inherited eye disease was initiated at the genetic outreach clinics conducted by the University of Cape Town (UCT) Department of Human Genetics at schools for visually and hearing-impaired children in the Western Cape. As a clinical registrar from 1992 to 1998, I accom panied Prof. Peter Beighton on numerous clinics, where I developed a fascination for understanding the genetic mechanisms underlying the sensory deficits affecting many of the children and their families. This led
more » ... o a research initiative into the molecular genetics of profound childhood deafness in South Africa, which became the topic of my PhD thesis. Prof. Beighton is an inspirational teacher and one of the first clinical genetics lectures he gave to medical students at UCT began with a whirlwind tour of genetic conditions around the world. One of the conditions he described was the X-linked eye condition Bornholm eye disease; and another, a severe autosomal form of colour blindness affecting the Indonesian islanders of Pingelap, whose disorder, achromatopsia, was caused by an early settler who carried a rare recessive founder mutation. So it was, with a sense of déjà vu, that over 20 years later at the University College of London (UCL) Institute of Ophthalmology, UK, I started a research project to evaluate the role of the cone opsins in a panel of British male patients at Moorfields Eye Hospital, London, with a variety of retinal eye conditions ranging from Bornholm eye disease to X-linked incomplete achromatopsia (blue cone monochromacy) and X-linked cone dystrophy. I present a synopsis of X-linked cone opsin disorders and review recent work on their phenotypes and genotypes. It gives me great pleasure as a former PhD student of Prof. Beighton's to write this article in his honour. X-linked cone photoreceptor disorders caused by mutations in the OPN1LW (L) and OPN1MW (M) cone opsin genes on chromosome Xq28 include a range of conditions from mild stable red-green colour vision deficiencies to severe cone dystrophies causing progressive loss of vision and blindness. Advances in molecular genotyping and functional analyses of causative variants, combined with deep retinal phenotyping, are unravelling genetic mechanisms underlying the variability of cone opsin disorders.
doi:10.7196/samj.2016.v106i6.11001 pmid:27245533 fatcat:ljp7efg3cracnplj2eazhf342e