Deep-phenotyping and further insights in ITM2B-related retinal dystrophy

PURPOSE:to reappraise the presentation and the course of the ITM2B-related retinal dystrophy (RD) and give further insights on ITM2B expression in the retina. METHODS:the clinical data of nine subjects with ITM2B-related RD were retrospectively reviewed. The genetic mutation was assessed for its influence on splicing in cultured fibroblasts. The cellular expression of ITM2B within the inner retina was investigated in wild-type mice through mRNA in-situ hybridization. RESULTS:all patients complained of decreased vision and mild photophobia around their twenties-thirties. Peculiar feature was the hyperreflective material on optical coherence tomography within the inner retina and the central outer nuclear layer with thinning of the retinal nerve fiber layer. While retinal imaging revealed very mild or no changes over the years, the VA slowly decreased with about one ETDRS letter per year. Finally, full-field electroretinography (ff-ERG) showed a mildly progressive inner retinal and cone dysfunction. ITM2B mRNA is expressed in all cellular types of the inner retina. Disease mechanism most likely involves mutant protein misfolding and/or modified protein interaction rather than misplicing. CONCLUSIONS:ITM2B-related RD is a peculiar, rare, slowly progressive retinal degeneration. Functional exams (ff-ERG and VA) seem more accurate in monitoring the progression in these patients, as imaging tends to be stable over the years.