IMPG2-related maculopathy

Purpose: To investigate the phenotype, variability and penetrance of IMPG2-related maculopathy. // Design: Retrospective observational case series. // Methods: Clinical evaluation, multimodal retinal imaging, genetic testing, and molecular modeling. // Results: Twenty-five individuals with a mono-allelic IMPG2 variant were included, 5 of whom were relatives of patients with IMPG2-associated retinitis pigmentosa. In 17 individuals (median age, 52 years; range, 20-72 years), a distinct maculopathy was present and included foveal elevation with or without subretinal vitelliform material or focal atrophy of the retinal pigment epithelium. Best corrected visual acuity (BCVA) was ≥ 20/50 in the better eye (n=15) and 5 patients were asymptomatic. Longitudinal observation (n=8, up to 19 years) demonstrated stable maculopathy (n=3), partial/complete resorption (n=4) or increase (n=1) of the subretinal material, with overall stable vision (n=6). The remaining 8 individuals (median age, 58 years; range, 43-83 years; BCVA ≥ 20/25) showed no manifest maculopathy and were identified through segregation analysis. All 8 were asymptomatic, with minimal foveal changes observed on optical coherence tomography in 3 cases. Eighteen different variants were detected, 11 of them truncating. Molecular modeling of five missense variants, c.727G>C, c.1124C>A, c.2816T>A, c.3047T>C and c.3193G>A supported the hypothesis that these have a loss-of-function effect. // Conclusions: Mono-allelic IMPG2 variants may result in haplo-insufficiency manifesting as a maculopathy with variable penetrance and expressivity. Family members of patients with IMPG2-related retinitis pigmentosa may present with vitelliform lesions. The maculopathy often remains limited to the fovea and is usually associated with moderate visual impairment

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Letter to the editor