Sir,

Peripherin/RDS is a structural transmembrane glycoprotein that contributes to the formation and stabilisation of rod and cone photoreceptor outer segment discs. Mutations in the peripherin/RDS gene can result in generalised retinal dystrophies or macular dystrophies1, 2 and are known to cause variable manifestations within families. We describe a novel mutation in exon 2 of the peripherin/RDS gene resulting in a three amino-acid deletion and causing a variable retinal phenotype within a three-generation family.

Case reports

Case 1

A 30-year-old man presented with a history of nyctalopia and reduced-peripheral visual fields. His best-corrected visual acuities were 6/6 in each eye. Anterior segments were normal on slit-lamp examination. Fundus examination revealed punctate hyperpigmentation in the peripheral retina (Figure 1). Colour vision was normal. Electroretinograms showed a reduction in light-adapted responses and markedly attenuated responses on dark adaptation.

Figure 1
figure 1

Posterior pole (a) and inferior nasal retinal view (b) of case 1.

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Case 2

A 61-year-old woman (mother of case 1) developed visual distortion at the age of 59. Initially when seen, she was found to have bilateral vitelliform macular changes associated with atrophy in the left eye. After 12 months, she developed haemorrhage, exudation and subretinal fluid at the right macula (Figure 2). Fundus fluorescein angiogram demonstrated a classic subretinal neovascular membrane, and photodynamic therapy was commenced (Figure 3). Electroretinogram showed a normal light- and dark-adapted responses and the Electro-oculogram was subnormal.

Figure 2
figure 2

Posterior pole of case 2 (a) Right eye showing haemorrhage in the right macula with fine exudates and possible subretinal fluid. (b) Left eye showing a vitelliform lesion with atrophic changes.

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Figure 3
figure 3

(a) Fundus fluorescein angiogram of case 2 showing the subretinal neovascular membrane in the right macula. (b) Angiogram of left macula.

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Case 3

The 86-year-old father of case 2 was diagnosed with retinitis pigmentosa many years ago and described poor vision since his 20s. According to him, his father also had poor vision for many years (Figure 4).

Figure 4
figure 4

Pedigree of the family with autosomal dominant inheritance with retinal and macular phenotypes.

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Mutation analysis of the coding region of the RDS/peripherin gene revealed c.618–626 del9 mutation in exon 2 of the RDS/peripherin gene in cases 1 and 2. This mutation deletes three amino acids p.207 Asp, 208 Gly, and 209 Val in frame.

Comment

Mutations involving these three amino acids have previously been reported causing autosomal dominant retinitis pigmentosa.3, 4 To our knowledge, this is the first report of this three amino-acid deletion that interestingly causes a highly variable phenotype within the same family. In addition, it highlights choroidal neovascularisation as a potential complication.