Original articleA Novel Mutation and Phenotypes in Phosphodiesterase 6 Deficiency
Section snippets
Imaging and Psychophysical Testing
Forty unrelated individuals with autosomal recessive RP were phenotyped. If applicable, additional family members were examined. Fundus photographs, optical coherence tomography [OCT], (Stratus and Cirrus; Zeiss, Jena, Germany), and fundus autofluorescence (AF) images were reviewed. AF was obtained by illuminating the fundus with argon laser light (488 nm) and viewing the resultant fluorescence through a bandpass filter with a short wavelength cutoff at 495 nm.22 Microperimetry (MP1; Nidek
Genetic Screening
Screening of 40 unrelated patients diagnosed with autosomal recessive or sporadic RP on the arRP array resulted in identification of at least one (out of two, as per definition of a recessive disease) possible disease-associated mutation in 32.5% of individuals (13/40). The likely disease-associated variants were identified in the following genes: PDE6A (R102C and N216S), PDE6B (D600N), CRB1 (T745M and P836T), USH2A (E478D, L555V, W4149R, P1978S, G713R, E767fs, and C759F), and RPE65 (A132T).
A
Discussion
Genetic heterogeneity in RP makes it challenging to advise patients regarding their visual prognoses. Genotyping and comprehensive phenotyping with ERG, AF, OCT, and MP1 mapping are helpful to specify prognosis and for gene-based treatment trials.3, 14, 29 Therefore, we applied a high-throughput genotyping array platform, electrophysiological testing, imaging, and psychophysical studies to genotype and phenotype patients with PDE6-related RP.
In one patient, AF imaging revealed abnormal foci of
Stephen H. Tsang, MD, PhD, is a Bernard-Becker-AUPO-Research to Prevent Blindness scholar and an Assistant Professor in Retina Division at New York-Presbyterian Hospital studying cyclic guanosine monophosphate-phosphodiesterase (PDE6), a key component of the phototransduction cascade. Dr Tsang's team provided evidence on how light induced posttranslational modification of PDE6 regulates signaling in the living retina. Dr Tsang generated lines of transgenic mice that provide models for testing
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Clinical findings of end-stage retinitis pigmentosa with a homozygous PDE6A variant (p.R653X)
2019, American Journal of Ophthalmology Case ReportsCitation Excerpt :Phenotypes in adult RP patients with the PDE6A variants exhibit similar clinical characteristics to our proband and these previously studied cases. These characteristics include onset in early childhood, retinal degeneration with bone spicule pigmentation from mid-peripheral to peripheral retina, attenuation of peripheral retinal vessels, distinguished ERG responses of both rod and cone function, and a severely constricted visual field until reaching their 20s–30s.6,7,19–22 Furthermore, macula involvements, which are often accompanied by macular edema and atrophy, have been reported in most of these types of cases.
AAV-mediated gene therapy halts retinal degeneration in PDE6β-deficient dogs
2016, Molecular TherapyCitation Excerpt :By the age of 40, patients present the ophthalmologic hallmarks of RP: attenuated retinal vessels, waxy-looking optic nerve heads, pigmentary changes in the mid- and far-peripheral retina, and atrophic maculopathy, in some cases with central remnants of normal retinal pigmented epithelium (RPE).8 Although some preservation of photopic responses may be observed, electroretinograms (ERGs) often fail to detect electrical activity.9 Optical coherence tomography (OCT) in patients carrying the null mutation in the β-subunit of PDE6 has also revealed massive photoreceptor loss and abnormal laminar architecture.10
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2016, Journal Francais d'Ophtalmologie
Stephen H. Tsang, MD, PhD, is a Bernard-Becker-AUPO-Research to Prevent Blindness scholar and an Assistant Professor in Retina Division at New York-Presbyterian Hospital studying cyclic guanosine monophosphate-phosphodiesterase (PDE6), a key component of the phototransduction cascade. Dr Tsang's team provided evidence on how light induced posttranslational modification of PDE6 regulates signaling in the living retina. Dr Tsang generated lines of transgenic mice that provide models for testing novel treatment approaches for patients with retinitis pigmentosa.