Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes.

Yu Fujinami-Yokokawa, Kaoru Fujinami, Angelos Kalitzeos, Michalis Georgiou, Anthony G Robson, Omar A Mahroo, Malena Daich Varela, Nikolas Pontikos, Michel Michaelides, Andrew R Webster, Thales A C de Guimarães

Journal: Progress in retinal and eye research 2024;100():101244

PMID: 38278208

Full Text on Elsevier Science View on PubMed

Abstract

Inherited retinal diseases (IRD) are a leading cause of blindness in the working age population and in children. The scope of this review is to familiarise clinicians and scientists with the current landscape of molecular genetics, clinical phenotype, retinal imaging and therapeutic prospects/completed trials in IRD. Herein we present in a comprehensive and concise manner: (i) macular dystrophies (Stargardt disease (ABCA4), X-linked retinoschisis (RS1), Best disease (BEST1), PRPH2-associated pattern dystrophy, Sorsby fundus dystrophy (TIMP3), and autosomal dominant drusen (EFEMP1)), (ii) cone and cone-rod dystrophies (GUCA1A, PRPH2, ABCA4, KCNV2 and RPGR), (iii) predominant rod or rod-cone dystrophies (retinitis pigmentosa, enhanced S-Cone syndrome (NR2E3), Bietti crystalline corneoretinal dystrophy (CYP4V2)), (iv) Leber congenital amaurosis/early-onset severe retinal dystrophy (GUCY2D, CEP290, CRB1, RDH12, RPE65, TULP1, AIPL1 and NMNAT1), (v) cone dysfunction syndromes (achromatopsia (CNGA3, CNGB3, PDE6C, PDE6H, GNAT2, ATF6), X-linked cone dysfunction with myopia and dichromacy (Bornholm Eye disease; OPN1LW/OPN1MW array), oligocone trichromacy, and blue-cone monochromatism (OPN1LW/OPN1MW array)). Whilst we use the aforementioned classical phenotypic groupings, a key feature of IRD is that it is characterised by tremendous heterogeneity and variable expressivity, with several of the above genes associated with a range of phenotypes.

Address: Moorfields Eye Hospital, London, United Kingdom; UCL Institute of Ophthalmology, University College London, London, United Kingdom; Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: [email protected].; Moorfields Eye Hospital, London, United Kingdom; UCL Institute of Ophthalmology, University College London, London, United Kingdom. Electronic address: [email protected].; Moorfields Eye Hospital, London, United Kingdom; UCL Institute of Ophthalmology, University College London, London, United Kingdom; Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. Electronic address: [email protected].; Moorfields Eye Hospital, London, United Kingdom; UCL Institute of Ophthalmology, University College London, London, United Kingdom. Electronic address: [email protected].; UCL Institute of Ophthalmology, University College London, London, United Kingdom; Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Department of Health Policy and Management, Keio University School of Medicine, Tokyo, Japan. Electronic address: [email protected].; Moorfields Eye Hospital, London, United Kingdom; UCL Institute of Ophthalmology, University College London, London, United Kingdom. Electronic address: [email protected].; Moorfields Eye Hospital, London, United Kingdom; UCL Institute of Ophthalmology, University College London, London, United Kingdom. Electronic address: [email protected].; Moorfields Eye Hospital, London, United Kingdom; UCL Institute of Ophthalmology, University College London, London, United Kingdom. Electronic address: [email protected].; Moorfields Eye Hospital, London, United Kingdom; UCL Institute of Ophthalmology, University College London, London, United Kingdom; Section of Ophthalmology, King s College London, St Thomas Hospital Campus, London, United Kingdom; Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom; Department of Translational Ophthalmology, Wills Eye Hospital, Philadelphia, PA, USA. Electronic address: [email protected].; Moorfields Eye Hospital, London, United Kingdom; UCL Institute of Ophthalmology, University College London, London, United Kingdom. Electronic address: [email protected].; Moorfields Eye Hospital, London, United Kingdom; UCL Institute of Ophthalmology, University College London, London, United Kingdom. Electronic address: [email protected].

DOI: 10.1016/j.preteyeres.2024.101244

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MeSH Terms: Humans, Cone-Rod Dystrophies, Eye Diseases, Hereditary, Genotype, Leber Congenital Amaurosis, Molecular Biology, Phenotype, Retinal Diseases