IMPG2-Related Maculopathy
Johannes Birtel1, Richard Caswell2, Samantha R De Silva3
1From the Oxford Eye Hospital (J.B., S.R.D.S., S.R., R.E.M., P.C.I.), Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; Nuffield Laboratory of Ophthalmology (J.B., S.R.D.S., S.R., R.E.M., P.C.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom; Department of Ophthalmology (J.B.), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Ophthalmology (J.B., P.H.), University of Bonn, Bonn, Germany.
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:
A total of 25 individuals with a mono-allelic IMPG2 variant were included, 5 of whom were relatives of patients with IMPG2-associated retinitis pigmentosa. A distinct maculopathy was present in 17 individuals (median age, 52 years; range, 20-72 years), 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). No manifest maculopathy was observed in 8 individuals (median age, 58 years; range, 43-83 years; BCVA ≥20/25), all were identified through segregation analysis. All 8 individuals were asymptomatic, with minimal foveal changes observed on optical coherence tomography in 3 cases. A total of 18 different variants were detected, 11 of them truncating. Molecular modeling of 5 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 haploinsufficiency 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.
More Related Videos
10:14Author Spotlight: Ex Vivo OCT-Based Multimodal Imaging of Human Donor Eyes for Research into Age-Related Macular Degeneration
Published on: May 26, 2023
05:14Author Spotlight: Overcoming Anti-VEGF Resistance Through Advanced Vascular Morphology Assessment in Choroidal Neovascularization
Published on: August 11, 2023