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Alberta A H J Thiadens, Anne E.D. de Boer, J Anneke Kievit, Virginie JM Verhoeven, Carel C B Hoyng, Ramon van Huet, Caroline Klaver; The clinical spectrum of IMPG2-associated retinal dystrophies. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2765.
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Mutations in the IMPG2 gene can lead to a variable clinical spectrum of retinal dystrophies, ranging from retinitis pigmentosa (RP) to adult-onset foveomacular vitelliform dystrophy (AFVD). With the development of gene-augmentation therapies, an in-depth understanding of the phenotypic spectrum, course and prognosis is important. We performed an observational clinical study to describe the natural history of IMPG2-associated retinal dystrophies.
11 patients from 6 families with IMPG2 mutations visited the ophthalmogenetic clinics in Rotterdam and Nijmegen. Ophthalmic examination included best-corrected visual acuity (BCVA) in Snellen, fundoscopy, color vision testing, Goldmann visual field testing, optical coherence tomography (OCT), fundus auto-fluorescence (FAF), and full-field electroretinography (ff-ERG). Age of onset and family history were recorded from medical files. We performed whole exome sequencing (WES) followed by segregation analyses. We evaluated visual prognosis with Kaplan Meier survival analyses.
The median follow-up time was 12 years (range 1-20). The mean age of onset was 43 years (range 31-58) and the mean age of WHO blindness (BCVA ≤ 0.10) was 66 years for AFVD. The RP patients (n=2) still had BCVA 0.50 at age >40 years. Patients with AFVD showed autofluorescent lipofuscin material in the fovea on FAF and OCT, intact peripheral visual fields, and normal photopic and scotopic responses on ff-ERG. The patients with RP showed no lipofuscin on FAF and OCT, had severe constricted visual fields, and absent photopic and scotopic responses on ff-ERG. WES analyses confirmed causal stopmutations in the IMPG2 gene in all patients. Segregation analyses confirmed an autosomal dominant (AD) inheritance mode in 5 families with AFVD, and an autosomal recessive (AR) pattern in 1 family with RP.
AD IMPG2 inheritance showed an AFVD phenotype, whereas AR inheritance caused RP in our families. It remains intriguing how mutations in the same gene can lead to these diverse clinical entities. Future gene therapy should take notice of a broader window of time for intervention in RP than in AFVD. For appropriate clinical counselling, one should be aware of the relevance of segregation analyses and family history in patients with IMPG2 mutations.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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