Sector Retinitis Pigmentosa: Extending the Molecular Genetics Basis and Elucidating the Natural History

• Published in: American journal of ophthalmology Vol. 221; pp. 299 - 310
• Main Authors: Georgiou, Michalis, Grewal, Parampal S., Narayan, Akshay, Alser, Muath, Ali, Naser, Fujinami, Kaoru, Webster, Andrew R., Michaelides, Michel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2021; Elsevier Limited; Elsevier Science
• Subjects: Adolescent; Adult; Age; Aged; Aged, 80 and over; Asymmetry; Cataracts; Disease; DNA Mutational Analysis; Electroretinography; Eye Proteins - genetics; Female; Fluorescein Angiography; Genes; Genetic Association Studies; Genetics; Humans; Male; Middle Aged; Molecular Biology; Natural history; Original; Patients; Pedigree; Retina; Retina - physiopathology; Retinitis Pigmentosa - diagnosis; Retinitis Pigmentosa - genetics; Retinitis Pigmentosa - physiopathology; Retrospective Studies; Symmetry; Tomography, Optical Coherence; Visual Acuity - physiology; Visual Field Tests; Visual Fields - physiology; Young Adult
• ISSN: 0002-9394; 1879-1891; 1879-1891
• DOI: 10.1016/j.ajo.2020.08.004

To determine the genetic background of sector retinitis pigmentosa (RP) natural history to better inform patient counseling. Retrospective case series. Review of clinical notes, retinal imaging including color fundus photography (CFP), fundus autofluorescence (FAF), optical coherence tomography (OCT), electrophysiological assessment (ERG), and molecular genetic testing were performed in patients with sector RP from a single tertiary referral center. Main outcomes measured were demographic data, signs and symptoms, visual acuity, molecular genetics; and ERG, FAF, and OCT findings. Twenty-six molecularly confirmed patients from 23 different families were identified harboring likely disease-causing variants in 9 genes. The modes of inheritance were autosomal recessive (AR, n=6: USH1C, n=2; MYO7A, n=2; CDH3, n=1; EYS, n=1), X-linked (XL, n=4: PRPS1, n=1; RPGR, n=3), and autosomal dominant (AD, n=16: IMPDH1, n=3; RP1, n=3; RHO, n=10), with a mean age of disease onset of 38.5, 30.5, and 39.0 years old, respectively. Five of these genes have not previously been reported to cause sector RP (PRPS1, MYO7A, EYS, IMPDH1, and RP1). Inferior and nasal predilection was common across the different genotypes, and patients tended to maintain good central vision. Progression on serial FAF was observed in RPGR, MYO7A, CDH23, EYS, IMPDH1, RP1, and RHO-associated sector RP. The genotypic spectrum of the disease is broader than previously reported. The longitudinal data provided will help to make accurate patient prognoses and counseling as well as inform patients' potential participation in the increasing numbers of trials of novel therapeutics and access to future treatments. •This is the largest series and longitudinal study in sector retinitis pigmentosa.•The genotypic spectrum of the disease is broader than previously reported.•The longitudinal data provided more accurate patient prognosis and counseling.•The study informed patients' potential participation in the increasing numbers of trials of novel therapeutics and access to future treatments.