Tomas S Aleman1,2,3, Erin C O'Neil1,2,3, Keli O'Connor1,2, Yu You Jiang1,2, Isabella A Aleman1,2, Jean Bennett1,2, Jessica I W Morgan1,2, Brian W Toussaint4,5. 1. Scheie Eye Institute at the Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 2. Center for Advanced Retinal and Ocular Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 3. Division of Ophthalmology of the Children's Hospital of Philadelphia, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 4. Christiana Care Health System, Wilmington, Delaware, USA. 5. Department of Ophthalmology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA.
Abstract
Purpose: To provide a detailed ophthalmic phenotype of two male patients with Bardet-Biedl Syndrome (BBS) due to mutations in the BBS7 gene Methods: Two brothers ages 26 (Patient 1, P1) and 23 (P2) underwent comprehensive ophthalmic evaluations over three years. Visual function was assessed with full-field electroretinograms (ffERGs), kinetic and chromatic perimetry, multimodal imaging with spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) with short- (SW) and near-infrared (NIR) excitation lights and adaptive optics scanning light ophthalmoscopy (AOSLO). Results: Both siblings had a history of obesity and postaxial polydactyly; P2 had diagnoses of type 1 Diabetes Mellitus, Addison's disease, high-functioning autism-spectrum disorder and -12D myopia. Visual acuities were better than 20/30. Kinetic fields were moderately constricted. Cone-mediated ffERGs were undetectable, rod ERGs were ~80% of normal mean. Static perimetry showed severe central cone and rod dysfunction. Foveal to parafoveal hypoautofluorescence, most obvious on NIR-FAF, co-localized with outer segment shortening/loss and outer nuclear layer thinning by SD-OCT, and with reduced photoreceptors densities by AOSLO. A structural-functional dissociation was confirmed for cone- and rod-mediated parameters. Worsening of the above abnormalities was documented by SD-OCT and FAF in P2 at 3 years. Gene screening identified compound heterozygous mutations in BBS7 (p.Val266Glu: c.797 T > A of maternal origin; c.1781_1783delCAT, paternal) in both patients.Conclusions: BBS7-associated retinal degeneration may present as a progressive cone-rod dystrophy pattern, reminiscent of both the murine and non-human primate models of the disease. Predominantly central retinal abnormalities in both cone and rod photoreceptors showed a structural-functional dissociation, an ideal scenario for gene augmentation treatments.
Purpose: To provide a detailed ophthalmic phenotype of two male patients with Bardet-Biedl Syndrome (BBS) due to mutations in the BBS7 gene Methods: Two brothers ages 26 (Patient 1, P1) and 23 (P2) underwent comprehensive ophthalmic evaluations over three years. Visual function was assessed with full-field electroretinograms (ffERGs), kinetic and chromatic perimetry, multimodal imaging with spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) with short- (SW) and near-infrared (NIR) excitation lights and adaptive optics scanning light ophthalmoscopy (AOSLO). Results: Both siblings had a history of obesity and postaxial polydactyly; P2 had diagnoses of type 1 Diabetes Mellitus, Addison's disease, high-functioning autism-spectrum disorder and -12D myopia. Visual acuities were better than 20/30. Kinetic fields were moderately constricted. Cone-mediated ffERGs were undetectable, rod ERGs were ~80% of normal mean. Static perimetry showed severe central cone and rod dysfunction. Foveal to parafoveal hypoautofluorescence, most obvious on NIR-FAF, co-localized with outer segment shortening/loss and outer nuclear layer thinning by SD-OCT, and with reduced photoreceptors densities by AOSLO. A structural-functional dissociation was confirmed for cone- and rod-mediated parameters. Worsening of the above abnormalities was documented by SD-OCT and FAF in P2 at 3 years. Gene screening identified compound heterozygous mutations in BBS7 (p.Val266Glu: c.797 T > A of maternal origin; c.1781_1783delCAT, paternal) in both patients.Conclusions: BBS7-associated retinal degeneration may present as a progressive cone-rod dystrophy pattern, reminiscent of both the murine and non-human primate models of the disease. Predominantly central retinal abnormalities in both cone and rod photoreceptors showed a structural-functional dissociation, an ideal scenario for gene augmentation treatments.
Authors: Akosua A Nti; Leona W Serrano; Harpal S Sandhu; Katherine E Uyhazi; Ilaina D Edelstein; Elaine J Zhou; Scott Bowman; Delu Song; Tara C Gangadhar; Lynn M Schuchter; Sheryl Mitnick; Alexander Huang; Charles W Nichols; Ravi K Amaravadi; Benjamin J Kim; Tomas S Aleman Journal: Retina Date: 2019-03 Impact factor: 4.256
Authors: Y Huang; A V Cideciyan; G I Papastergiou; E Banin; S L Semple-Rowland; A H Milam; S G Jacobson Journal: Invest Ophthalmol Vis Sci Date: 1998-11 Impact factor: 4.799
Authors: Monika K Grudzinska Pechhacker; Samuel G Jacobson; Arlene V Drack; Matteo Di Scipio; Ine Strubbe; Wanda Pfeifer; Jacque L Duncan; Helene Dollfus; Nathalie Goetz; Jean Muller; Andrea L Vincent; Tomas S Aleman; Anupreet Tumber; Caroline Van Cauwenbergh; Elfride De Baere; Emma Bedoukian; Bart P Leroy; Jason T Maynes; Francis L Munier; Erika Tavares; Eman Saleh; Ajoy Vincent; Elise Heon Journal: Invest Ophthalmol Vis Sci Date: 2021-12-01 Impact factor: 4.799