Imran H Yusuf, Johannes Birtel, Morag Shanks, Penny Clouston, Susan M. Downes, Peter Charbel Issa, Robert E MacLaren
Abstract
Purpose : SNRNP200 is a gene recently identified as a cause of autosomal dominant retinitis pigmentosa (RP). The aim of this study was to report novel disease-associated variants and describe the retinal phenotype in patients with RP due to variants in SNRNP200, a gene encoding a ubiquitously expressed protein important in pre-mRNA splicing.
Methods : A cross-sectional descriptive study involving patients identified from two tertiary referral retinal genetics clinics. 9 consecutive patients from 8 families with RP attributed to variants in SNRNP200 were included. Genetic diagnoses were established with molecular genetic testing using targeted next-generation sequencing. All patients underwent full clinical ophthalmic evaluation, retinal imaging with spectral-domain optical coherence tomography, short wavelength fundus autofluorescence (Heidelberg Spectralis) and digital colour fundus photography.
Results : 9 patients were included in the study, 4 of whom were female, aged between 16 and 55 years of age. Each patient presented with symptoms and signs typical of a rod-cone dystrophy. Retinal imaging characteristics are presented in Figure 1. There was no suggestion of any systemic or syndromic features. Disease onset was commonly seen in childhood, although two patients experienced symptom onset in middle age (range 4 to 53 years). Progression of retinal degeneration was slow: 7 patients had a best corrected visual acuity of better than 20/40 in the better seeing eye at last follow-up (age 16 to 55), although two patients developed macular oedema. Molecular genetic testing revealed 2 novel variants (c.1547G>T p.(Cys516Phe) and c.2359G>A p.(Ala787Thr)) and 7 previously described variants in SNRNP200, all of which were missense variants. Both novel variants are well conserved, segregate with disease in affected families and are predicted to be disease causing in silico.
Conclusions : Variants in SNRNP200 result in non-syndromic rod-cone dystrophy characterized clinically by a variable age of symptom onset with a retinal phenotype typical of RP.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.