TY  - JOUR
KW  - Humans
KW  -  Male
KW  -  Female
KW  -  Middle Aged
KW  -  Adult
KW  -  Visual Acuity
KW  -  Retrospective Studies
KW  -  Tomography
KW  -  Optical Coherence
KW  -  Electroretinography
KW  -  Aged
KW  -  Pedigree
KW  -  Young Adult
KW  -  Guanylate Cyclase
KW  -  Mutation
KW  -  DNA Mutational Analysis
KW  -  Fluorescein Angiography
KW  -  Adolescent
KW  -  Retinal Diseases
A1  - Allon, Gilad
A1  - Lin, Siying
A1  - Robson, Anthony G
A1  - Arno, Gavin
A1  - Neveu, Magella M
A1  - Hysi, Pirro G
A1  - Michaelides, Michel
A1  - Webster, Andrew R
A1  - Mahroo, Omar A
JF  - Investigative Ophthalmology & Visual Science (IOVS)
UR  - https://doi.org/10.1167/iovs.66.2.50
PB  - Association for Research in Vision and Ophthalmology (ARVO)
ID  - discovery10205568
N2  - PURPOSE: To report findings in GUCA1A-associated retinopathy, a rare autosomal-dominant retinopathy. METHODS: Clinical features and investigations from molecularly confirmed patients at a large referral center were analyzed (retrospective cohort study). RESULTS: Nineteen patients (14 families), with five different variants, were included: p.(Tyr99Cys) in 10 families and p.(Leu84Phe), p.(Ile107Thr), p.(Glu111Ala), and p.(leu176Phe) in 1 family each. Mean (SD) ages at first and last visits were 38 (17) and 48 (15) years, respectively. Mean (SD) logMAR visual acuities at the first and last visits were 0.67 (0.61) and 0.94 (0.58) for right eyes and 0.63 (0.63) and 0.95 (0.74) for left eyes. Acuities ranged from 0.00 logMAR to no light perception. Most described progressive problems with central and color vision. Across 144 patient visits, logMAR acuity correlated with age (Spearman coefficients of 0.43 and 0.54 for right and left eyes, P < 0.001), with a high interocular correlation (coefficient 0.90, P < 0.001). Optical coherence tomography showed irregularity and then loss of the central ellipsoid zone. Ultra-widefield imaging showed peripheral degeneration in some patients. Electrophysiology (n = 13) was consistent with cone dystrophy (n = 11) or macular dystrophy (n = 2). Compared with the common p.(Tyr99Cys) variant, patients with p.(Glu111Ala) (n = 2) had worse vision; those with p.(Leu84Phe) (n = 3) were younger with earlier-onset visual loss. Patients with p.(Ile107Thr) (n = 2) showed later presentation, with milder acuity reduction. CONCLUSIONS: We present genotypic and phenotypic findings from the largest cohort with GUCA1A retinopathy. Most had progressive visual loss and electrophysiologic evidence of cone dystrophy. Possible genotype-phenotype correlations emerged, but subgroups were small for four of five variants.
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IS  - 2
AV  - public
VL  - 66
Y1  - 2025/02/03/
TI  - Clinical, Genetic, Imaging and Electrophysiological Findings in a Cohort of Patients With GUCA1A-Associated Retinopathy
ER  -