Homozygous ROM1 frameshift variant associated with late-onset retinal dystrophy

In the human retina, ROM1 and PRPH2 interact to form and maintain the photoreceptor outer segment. While numerous PRPH2 variants have been associated with a wide spectrum of inherited retinal diseases, monogenic ROM1-associated retinopathy appears to be exceptionally rare. Here, we describe the clinical and genetic findings of a patient with late-onset retinal dystrophy carrying a homozygous ROM1 frameshift variant.

Clinical assessment included multimodal imaging with blue-light and near-infrared fundus autofluorescence as well as spectral-domain optical coherence tomography. Genetic testing was performed using long-read whole-genome sequencing, followed by phenotype-driven variant analysis.

A 62-year-old man presented with subjective visual difficulties and a best-corrected visual acuity of 20/25 in both eyes. Fundus autofluorescence revealed diffuse hyper- and hypoautofluorescent flecks extending from the macula beyond the vascular arcades with relative peripapillary sparing. Spectral-domain optical coherence tomography demonstrated perifoveal thinning of the outer retinal layers and hyperreflective irregularities at the level of the retinal pigment epithelium. Genetic testing identified a homozygous likely pathogenic frameshift variant in ROM1: c.332_338delinsCCCCCCCAGCACCA, p.(Gly111Alafs*23).

This case adds to the evidence that biallelic ROM1 variants can independently cause retinal dystrophy and should be considered in the differential diagnosis of late-onset flecked retinopathies.