Clinical Phenotype of <i>PDE6B</i>-Associated Retinitis Pigmentosa

• Main Authors: Laura Kuehlewein, Ditta Zobor, Katarina Stingl, Melanie Kempf, Fadi Nasser, Antje Bernd, Saskia Biskup, Frans P.M. Cremers, Muhammad Imran Khan, Pascale Mazzola, Karin Schäferhoff, Tilman Heinrich, Tobias B. Haack, Bernd Wissinger, Eberhart Zrenner, Nicole Weisschuh, Susanne Kohl
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: International Journal of Molecular Sciences
• Subjects: retinitis pigmentosa; phosphodiesterase 6
• Online Access: https://www.mdpi.com/1422-0067/22/5/2374

In this retrospective, longitudinal, observational cohort study, we investigated the phenotypic and genotypic features of retinitis pigmentosa associated with variants in the <i>PDE6B</i> 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 <i>PDE6B</i> 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 <i>PDE6B</i> variants found in our patients were novel. Thus, this study contributed substantially to the <i>PDE6B</i> 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 <i>PDE6B</i>-related retinitis pigmentosa (RP) clinical trials.