Dataset Information

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.

SUBMITTER: Kuehlewein L

PROVIDER: S-EPMC7956818 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Kuehlewein Laura L Zobor Ditta D Stingl Katarina K Kempf Melanie M Nasser Fadi F Bernd Antje A Biskup Saskia S Cremers Frans P M FPM Khan Muhammad Imran MI Mazzola Pascale P Schäferhoff Karin K Heinrich Tilman T Haack Tobias B TB Wissinger Bernd B Zrenner Eberhart E Weisschuh Nicole N Kohl Susanne S

International journal of molecular sciences 20210227 5

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 autofluorescen ...[more]

PMID: 33673512

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Project description:ImportanceSNRNP200 is a recently identified genetic cause of autosomal dominant retinitis pigmentosa (RP). However, the associated retinal phenotype is not well characterized.ObjectiveTo describe the retinal phenotype in patients with RP secondary to variants in SNRNP200.Design, setting, and participantsThis retrospective, case-series study was performed at 2 tertiary referral centers for inherited retinal diseases. Participants included 9 consecutive patients from 8 families with RP attributed to variants in SNRNP200. Data were collected from August 2017 to March 2018 and analyzed from May to July 2018.Main outcomes and measuresResults of clinical evaluation, multimodal retinal imaging, and molecular genetic testing using targeted next-generation sequencing.ResultsOf the 9 patients included in the analysis (4 female and 5 male; mean [SD] age at presentation, 19 [15] years), each presented with nyctalopia, typically in the first 2 decades of life, although 2 patients experienced symptom onset in middle age. None had any consistent systemic features suggestive of syndromic RP. Retinal imaging studies and electroretinography findings were typical of a rod-predominant dystrophy with later involvement of cone photoreceptors. Phenotypic heterogeneity was typified by 4 unrelated patients with the common c.2041C>T SNRNP200 variant who demonstrated a variable age of disease onset (middle teenage years to the fourth decade of life). Disease progression was slow, with all but 1 patient maintaining visual acuity of better than 20/40 in the better-seeing eye in the fifth and sixth decades of life.Conclusions and relevanceThese data suggest that variants in SNRNP200 result in nonsyndromic RP with a typical phenotype of a rod-predominant dystrophy. Significant phenotypic heterogeneity and nonpenetrance were noted within some affected families. Symptom onset was typically within the first 2 decades of life, with slow progression and well-preserved visual acuities into the fifth and sixth decades.

Dataset Information

Clinical Phenotype of PDE6B-Associated Retinitis Pigmentosa.

Publications

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

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