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The term “pattern dystrophy” (PD) of the retina refers to a group of inherited dystrophies characterised by deposition of abnormal pigment at the level of retinal pigment epithelium (RPE).1
Here we report the clinical features of an Italian family (fig 1) affected by autosomal dominant PD associated with a new mutation in the RDS gene.
The proband I-1 is a 76 year old man who referred with progressive reduction of visual acuity at approximately 50 years of age; he showed an uncorrected visual acuity of 20/400 in the right eye and 20/100 in the left eye in lateral gaze position. Examination of the retina showed pink optic nerve heads, normal retinal vessels, retinal pigmented epithelial, and choriocapillaris atrophy in the peripapillary regions bilaterally and an extensive geographic atrophy that involved the posterior pole within the vascular arcades clearly demarcated from healthy appearing tissue in the periphery (fig 2A). Confocal scanning laser ophthalmoscope (cSLO) fundus autofluorescence imaging showed a central well circumscribed loss of autofluorescence corresponding to the atrophic area. Patient I-1 had abnormal rod and cone electroretinogram (ERG) responses (scotopic blue flash: 166 μV; normal 379 (SD 104) μV photopic: 43.5 μV; normal 210 (86) μV.
The electro-oculogram (EOG) cannot be performed.
Patient II-1, a 46 year old woman, at examination did not have any subjective visual complaint. She presented with a best corrected visual acuity of 20/20 in the right eye with a refraction of −0.75D, and 20/20 in the left eye uncorrected. At fundus examination, she showed a normal optic disc and retinal vessels in both eyes, with a characteristic yellowish subfoveal lesion with five “butterfly-shaped” radiating arms. On autofluorescence imaging, the funduscopic yellowish linear deposits in macular region are shown to be more fluorescent than the background (fig 2B). The yellowish butterfly-shaped lesions correspond to a radial hypofluorescence in the macular area, enclosed by a faint hyperfluorescence, revealed by fluorescein angiography.
Scotopic ERG tracing was reduced at 185 μV while the photopic tracing was in the normal range at 135 μV; the EOG revealed a decreased Arden ratio (RE 1.53; LE 1.60; normal ratio >1.65).
Patient II-2, a 45 year old woman, at 44 years of age complained of metamorphopsia, and 1 year later she reported a reduced clarity of central vision. At examination, she had a visual acuity of 20/20 in both eyes. Amsler grid test revealed a waviness in the central field of the right eye. Fundus examination demonstrated normal disc and vessels. The perifoveal region had a lightly yellowish spots clustered at the level of the foveal and perifoveal area; the periphery was of healthy appearance. On autofluorescence imaging the macular lesions showed a high level of autofluorescence that better defined the abnormalities observed by ophthalmoscopy.
A fluorescein angiogram showed a hypofluorescent area in the macular region with a hyperfluorescent halo. There was a normal ERG (scotopic blue flash: 376 μV; photopic: 218 μV) and EOG such as colour vision testing.
Genotype analysis revealed a 497G→A transition in the exon 1 of the RDS gene leading to the amino acid change G167S. This base substitution segregated with the phenotype disease in all three affected family members and was not present in 50 unrelated control subjects.
The new mutation, described here, lies very close to the cysteine position 165 and 166 residues that have been suggested to be important for the ability of the peripherin protein to keep normal flattened outer segment disc morphology.8
The morphological changes associated with RDS mutations causing pattern dystrophies of the macula ranged from mild depigmentation of the fovea to advanced geographic atrophy or choroidal neovascularisation.6,9,10
In this study the two younger patients (II-1 and II-2) showed typical lesions of “butterfly-shaped” pattern dystrophy while the oldest one (I-1) had a severe geographic atrophy of the retina probably as an advanced evolution of lesions showed by his daughters.
The missense mutation in the RDS gene described in this report is associated with a relatively severe manifestation of PD in affected family members. The identification and further characterisation of mutations in the RDS gene may yield insight into the function of the peripherin protein, the pathogenesis of PD and other retinal dystrophies, and the development of treatment for these disabling visual disorders.
Grant support (FS and ER) PRIN 2002 COFIN–MURST.
Competing interests: none declared