Danial Roshandel1,2, Jennifer A Thompson3, Jason Charng1,2, Dan Zhang1,2, Enid Chelva3, Sukanya Arunachalam1,2, Mary S Attia1,2, Tina M Lamey1,3, Terri L McLaren1,3, John N De Roach1,3, David A Mackey1,2,3, Steve D Wilton4,5, Sue Fletcher4,5, Samuel McLenachan1,2, Fred K Chen1,2,3,6,7. 1. Centre for Ophthalmology and Visual Science, The University of Western Australia , Perth, Australia. 2. Ocular Tissue Engineering Laboratory, Lions Eye Institute , Nedlands, Australia. 3. Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital , Nedlands, Australia. 4. Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University , Murdoch, Australia. 5. The Perron Institute, The University of Western Australia , Nedlands, Australia. 6. Department of Ophthalmology, Royal Perth Hospital , Perth, Australia. 7. Department of Ophthalmology, Perth Children's Hospital , Nedlands, Australia.
Abstract
BACKGROUND: Mutations in the splicing factor pre-messenger RNA processing factor 31 (PRPF31) gene cause autosomal dominant retinitis pigmentosa 11 (RP11) through a haplo-insufficiency mechanism. We describe the phenotype and progression of microperimetry and autofluorescence endpoints in an Indigenous Australian RP11 family. PATIENTS AND METHODS: Ophthalmic examination, optical coherence tomography, fundus autofluorescence and microperimetry were performed at baseline and every 6-12 months. Baseline and annual change in best-corrected visual acuity (BCVA), microperimetry mean sensitivity (MS) and number of scotoma loci, residual ellipsoid zone (EZ) span and hyperautofluorescent ring (HAR) area were reported. Next-generation and Sanger sequencing were performed in available members. RESULTS: 12 affected members from three generations were examined. Mean (SD, range) age at onset of symptoms was 11 (4.5, 4-19) years. MS declined steadily from the third decade and EZ span and HAR area declined rapidly during the second decade. Serial microperimetry showed negligible change in MS over 2-3 years. However, mean EZ span, near-infrared and short-wavelength HAR area reduction was 203 (6.4%) µm/year, 1.8 (8.7%) mm2/year and 1.1 (8.6%) mm2/year, respectively. Genetic testing was performed on 11 affected and 10 asymptomatic members and PRPF31 c.1205 C > A (p.Ser402Ter) mutation was detected in all affected and two asymptomatic members (non-penetrant carriers). CONCLUSIONS: Our findings suggest that in the studied cohort, the optimal window for therapeutic intervention is the second decade of life and residual EZ span and HAR area can be considered as efficacy outcome measures. Further studies on larger samples with different PRPF31 mutations and longer follow-up duration are recommended.
BACKGROUND: Mutations in the splicing factor pre-messenger RNA processing factor 31 (PRPF31) gene cause autosomal dominant retinitis pigmentosa 11 (RP11) through a haplo-insufficiency mechanism. We describe the phenotype and progression of microperimetry and autofluorescence endpoints in an Indigenous Australian RP11 family. PATIENTS AND METHODS: Ophthalmic examination, optical coherence tomography, fundus autofluorescence and microperimetry were performed at baseline and every 6-12 months. Baseline and annual change in best-corrected visual acuity (BCVA), microperimetry mean sensitivity (MS) and number of scotoma loci, residual ellipsoid zone (EZ) span and hyperautofluorescent ring (HAR) area were reported. Next-generation and Sanger sequencing were performed in available members. RESULTS: 12 affected members from three generations were examined. Mean (SD, range) age at onset of symptoms was 11 (4.5, 4-19) years. MS declined steadily from the third decade and EZ span and HAR area declined rapidly during the second decade. Serial microperimetry showed negligible change in MS over 2-3 years. However, mean EZ span, near-infrared and short-wavelength HAR area reduction was 203 (6.4%) µm/year, 1.8 (8.7%) mm2/year and 1.1 (8.6%) mm2/year, respectively. Genetic testing was performed on 11 affected and 10 asymptomatic members and PRPF31 c.1205 C > A (p.Ser402Ter) mutation was detected in all affected and two asymptomatic members (non-penetrant carriers). CONCLUSIONS: Our findings suggest that in the studied cohort, the optimal window for therapeutic intervention is the second decade of life and residual EZ span and HAR area can be considered as efficacy outcome measures. Further studies on larger samples with different PRPF31 mutations and longer follow-up duration are recommended.
Authors: Danial Roshandel; Rachael C Heath Jeffery; Jason Charng; Danuta M Sampson; Samuel McLenachan; David A Mackey; Fred K Chen Journal: Transl Vis Sci Technol Date: 2021-12-01 Impact factor: 3.283
Authors: Samuel McLenachan; Dan Zhang; Janya Grainok; Xiao Zhang; Zhiqin Huang; Shang-Chih Chen; Khine Zaw; Alanis Lima; Luke Jennings; Danial Roshandel; Sang Yoon Moon; Rachael C Heath Jeffery; Mary S Attia; Jennifer A Thompson; Tina M Lamey; Terri L McLaren; John De Roach; Sue Fletcher; Fred K Chen Journal: Genes (Basel) Date: 2021-09-28 Impact factor: 4.096
Authors: Danial Roshandel; Jennifer A Thompson; Rachael C Heath Jeffery; Dan Zhang; Tina M Lamey; Terri L McLaren; John N De Roach; Samuel McLenachan; David A Mackey; Fred K Chen Journal: Genes (Basel) Date: 2021-06-14 Impact factor: 4.096