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Expanded Retinal Disease Spectrum Associated With Autosomal Recessive Mutations in GUCY2D
Journal article   Peer reviewed

Expanded Retinal Disease Spectrum Associated With Autosomal Recessive Mutations in GUCY2D

Maria L Stunkel, Scott E Brodie, Artur V Cideciyan, Wanda L Pfeifer, Elizabeth L Kennedy, Edwin M Stone, Samuel G Jacobson and Arlene V Drack
American journal of ophthalmology, Vol.190, pp.58-68
06/2018
DOI: 10.1016/j.ajo.2018.03.021
PMID: 29559409

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Abstract

GUCY2D has been associated with autosomal recessive Leber congenital amaurosis and autosomal dominant cone-rod dystrophy. This report expands the phenotype of autosomal recessive mutations to congenital night blindness, which may slowly progress to mild retinitis pigmentosa. Retrospective case series. Multicenter study of 5 patients (3 male, 2 female). All patients presented with night blindness since childhood. Age at referral was 9-45 years. Length of follow-up was 1-7 years. Best-corrected visual acuity at presentation ranged from 20/15 to 20/30 and at most recent visit averaged 20/25. No patient had nystagmus or high refractive error. ISCEV standard electroretinography revealed nondetectable dark-adapted dim flash responses and reduced amplitude but not electronegative dark-adapted bright flash responses with similar waveforms to the reduced-amplitude light-adapted single flash responses. The 30 Hz flicker responses were relatively preserved. Macular optical coherence tomography revealed normal lamination in 3 patients, with abnormalities in 2. Goldmann visual fields were normal at presentation in children but constricted in 1 adult. One child showed loss of midperipheral fields over time. Fundus appearance was normal in childhood; the adult had sparse bone spicule-like pigmentation. Full-field stimulus testing (FST) revealed markedly decreased retinal sensitivity to light. Dark adaptation demonstrated lack of rod-cone break. Two patients had tritanopia. All 5 had compound heterozygous mutations in GUCY2D. Three of the 5 patients harbor the Arg768Trp mutation reported in GUCY2D-associated Leber congenital amaurosis. Autosomal recessive GUCY2D mutations may cause congenital night blindness with normal acuity and refraction, and unique electroretinography. Progression to mild retinitis pigmentosa may occur.
Visual Fields - physiology Humans Middle Aged Male Cone-Rod Dystrophies - genetics Dark Adaptation Female Genetic Diseases, X-Linked - genetics Retrospective Studies Refraction, Ocular - physiology Child Night Blindness - genetics Visual Acuity - physiology Electroretinography Retinitis Pigmentosa - genetics Leber Congenital Amaurosis - genetics Genes, Recessive Eye Diseases, Hereditary - genetics Myopia - genetics Adolescent Guanylate Cyclase - genetics Visual Field Tests Mutation Photic Stimulation Receptors, Cell Surface - genetics

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