Clinical Phenotype of PDE6B-Associated Retinitis Pigmentosa

Abstract

In this retrospective, longitudinal, observational cohort study, we investigated the phenotypic and genotypic features of retinitis pigmentosa associated with variants in the PDE6B gene. Patients underwent clinical examination and genetic testing at a single tertiary referral center, including best-corrected visual acuity (BCVA), kinetic visual field (VF), full-field electroretinography, full-field stimulus threshold, spectral domain optical coherence tomography, and fundus autofluorescence imaging. The genetic testing comprised candidate gene sequencing, inherited retinal disease gene panel sequencing, whole-genome sequencing, and testing for familial variants by Sanger sequencing. Twenty-four patients with mutations in PDE6B from 21 families were included in the study (mean age at the first visit: 32.1 ± 13.5 years). The majority of variants were putative splicing defects (8/23) and missense (7/23) mutations. Seventy-nine percent (38/48) of eyes had no visual acuity impairment at the first visit. Visual acuity impairment was mild in 4% (2/48), moderate in 13% (6/48), and severe in 4% (2/48). BCVA was symmetrical in the right and left eyes. The kinetic VF measurements were highly symmetrical in the right and left eyes, as was the horizontal ellipsoid zone (EZ) width. Regarding the genetic findings, 43% of the PDE6B variants found in our patients were novel. Thus, this study contributed substantially to the PDE6B mutation spectrum. The visual acuity impairment was mild in 83% of eyes, providing a window of opportunity for investigational new drugs. The EZ width was reduced in all patients and was highly symmetric between the eyes, making it a promising outcome measure. We expect these findings to have implications on the design of future PDE6B-related retinitis pigmentosa (RP) clinical trials.

Novel variants in PDE6A and PDE6B genes and its phenotypes in patients with retinitis pigmentosa in Chinese families

“…OCT images showed a major reduction in the ONL and the EZ width, indicating the progression of the disease. Similar results were previously shown by others [ 26 , 28 , 29 ]. In 8 patients of different ages, at the age of 12 we can still observe some ONL and the EZ looks almost normal.…”

“…Several complications of macula due to PDE6A or PDE6B mutations were noted in our patients, mainly in older ages. CME was present in 6.25%, less than studies in PDE6A (25%) and PDE6B (35%) by Kuehlewein but similar to that in the general population of patients with RP [ 27 , 28 , 30 – 32 ]. ERM in 56% (50% in PDE6A and 66.6% in PDE6B), similar to Kuehlewein’s study about PDE6B (67%), higher than Kuehlewein’s study about PDE6A.…”

Novel Variants in Phosphodiesterase 6A and Phosphodiesterase 6B Genes and Its Phenotypes in Patients With Retinitis Pigmentosa in Chinese Families

“…variants and three with PDE6B variants, all of our patients complaint night blindness since the memory which consistent with previous studies that reveal that nyctalopia occurs in early childhood [9,[29][30][31][32][33].ERG presenting extinguish in most cases or only 30Hz mild reserved in previous studies [9,29,31,32,34] ,and we come to the same conclusion. The EZ width was reduced in all patients and was highly symmetric between the eyes [35][36][37], and we come to the same conclusion. When it comes to the complications of PDE6A and PDE6B variants, the most worth to pay attention to being macular abnormalities, such as vitreomacular traction, epiretinal membrane, cystoid macular edema, retinoschisis lamellar macular hole.…”

Using cGMP analogues to modulate photoreceptor light sensitivity: Perspectives for the treatment of retinal degeneration

“…Nevertheless, one has to be aware of possible challenges arising due to the genetic heterogeneity of different RP forms, different cGMP levels in the diseased cells and different kinetics of the disease development ( 17, 43 ). Still to be determined is the effect of this cGMP-analogues combination also on other CNG-channel isoforms ( e.g .…”