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Helena Margaret Anthonia Feenstra, Mital Shah, Morag Shanks, Robert E MacLaren, Penny Clouston, Susan Downes; Usher genes; from a clinical and genetic perspective. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2341.
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To analyse the phenotype and genotype of patients referred with Usher syndrome from the clinical service and to compare this with data from all patients with genetic variants in Usher genes identified by the genetics laboratory.
Case notes of patients with a diagnosis of Usher syndrome were reviewed and phenotype-genotype correlation was performed (Group A). Simultaneously, genetic data from the clinical laboratory was interrogated for all disease causing variants identified in Usher syndrome genes; the clinical records for these patients were also reviewed to carry out phenotype-genotype correlation (Group B).Clinical data included: age at onset of ocular symptoms, self-reported hearing impairment, area of remaining Goldmann visual field and spectral domain optical coherence tomography (OCT) images. Next generation sequencing (NGS) gene panel based testing was carried out on the Oxford retinitis pigmentosa (RP) and Syndromic RP panels.
47 patients had a clinical diagnosis of Usher syndrome (Group A) (mean age 39 yrs, 64% male). Of these patients, 37 (79%) had a molecularly confirmed diagnosis (Figure 1).In group B 129 patients were identified with pathogenic variants in Usher genes (mean age 41 yrs, 55% male), of which 61 patients (47%) had a molecularly confirmed diagnosis of either Usher syndrome (n = 37, mean age 39 yrs) or simplex RP (n = 24, mean age 45 yrs) (Figure 2). All molecularly confirmed diagnoses of simplex RP were associated with USH2A.The mean age at onset of first ocular symptoms in group B was 15 yrs for Usher syndrome (range 5-63, SD 11.3) and 32 yrs for simplex RP (range 16-65, SD 14.6) (p<0.001). Cystoid macular oedema on OCT was present in 8/23 (34.8%) Usher patients and 1/20 (0.5%) simplex RP patients. Patients with Usher syndrome had a smaller surviving area of visual field for isopter III4e than patients with simplex RP; 5023 mm2 (n=29 eyes, SD 5879) vs 8798 mm2 (n=22 eyes, SD 6405), p=0.03. The mean Snellen visual acuity in LogMAR was 0.61 or (n=71 eyes, SD 0.79) and 0.33 or (n=46 eyes SD 0.56) in the Usher and simplex RP group respectively (p=0.04).
With the advent of NGS, variants in genes hitherto only associated with specific phenotypes have been described with expanded phenotypes. USH2A is a typical example of this. In patients with USH2A non syndromic RP have later onset of disease, better visual acuities and better visual field preservation than patients with Usher syndrome.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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