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Ajoy Vincent, Elise Heon; Phenotypic Characterization Of Autosomal Dominant Macular Dystrophy In A Family With Novel Inframe Deletion In GUCY2D. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4536.
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© ARVO (1962-2015); The Authors (2016-present)
To report detailed phenotypic characteristics of autosomal dominant macular dystrophy associated with short deletion in GUCY2D
Five members of a family (aged: 7 - 44 years) including four affected underwent detailed ophthalmological evaluation that included distance and color vision testing, contrast sensitivity measurement and fundus photography. Fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT) and full-field electroretinography (ERG) was performed in all affected cases. Sensory electro-oculography (EOG) was performed when possible (n = 2). The DNA of the proband or at least one affected member was sequenced for mutations in PRPH2, BEST1, PROM1, GUCY2D, RIMS1, SEMA4A and ELOVL4 genes. The GUCY2D exon 2 harboring the variant of interest was amplified and sequenced in all available family members. The allele- frequency of the novel change was assessed in 300 ethnically matched control chromosomes.
The best-corrected visual acuity was ≥20/50 in all cases except for in the left eye of case II9. The contrast sensitivity was normal (1.65 log units) in all eyes with vision ≥20/50. Fundus photography showed macular pigmentary changes in a patterned fashion in three cases. The left eye case II9 that had poor vision (20/400) had disciform macular scar with chorioretinal atrophy. The FAF imaging showed areas of hypofluorescence underlying the pigmentary changes with adjacent areas of increased fluorescence. The OCT demonstrated discrete areas of hypo and hyper-reflective deposition at the level of the retinal pigment epithelium (RPE) in all affected. The ERG was either normal or showed cone-rod pattern of abnormality. The EOG showed decreased Ardens ratio in the two tested. A heterozygous novel six nucleotide deletion c.129_134delTCTGCT (p.Leu43del6) was identified in the proband and it segregated with the disease phenotype; the change was not observed in controls. No mutations were found in PRPH2, BEST1, PROM1, RIMS1, SEMA4A and ELOVL4 .
This is the first report of a deletion in GUCY2D to cause dominant macular dystrophy phenotype. The visual parameters appear to relatively stable even in adults unless there is macular atrophy. The OCT shows abnormalities at the level of RPE and the ERG commonly show predominant involement of cone system.
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