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A. Gal, A. Schuster, E. Schmid, R. Wilke, A.R. Janecke, B. Wissinger, D.A. Thompson, E. Zrenner; The Phenotype of Early–Onset Retinal Degeneration in Patients With RDH12 Mutations . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2975.
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© ARVO (1962-2015); The Authors (2016-present)
To describe the retinal dystrophy phenotype associated with mutations in RDH12, the gene encoding a retinoid dehydrogenase/reductase thought to function in the visual cycle.
A total of 16 individuals (age 4–69 years) from 13 families with RDH12 mutations were studied. Retinal phenotypes were characterized by clinical examination, Goldmann perimerty, Panel D15 testing, dark–adapted final thresholds, and Ganzfeld and multifocal electroretinography (ERG).
Patients carried RDH12 mutations in homozygous (p.G127X, p.H151D, p.Q189X, p.Y226C, p.Ala269GlyfsX1, and p.L274P) or compound heterozygous (p.H151D/p.T155I, p.H151D/p.Ala269GlyfsX1, and p.R65X/p.Ala269GlyfsX1) form. Primary diagnosis was made in early childhood by documenting poor yet useful visual function with visual field constriction, loss of visual acuity, and night blindness. Nystagmus and photophobia were infrequent. Pronounced maculopathy was noted in 13 patients. Bone–spicules were present in 15 patients, with mild hyperpigmentation observable even in children. In young individuals (3, 7, and 9 years), diminished yet significantly preserved rod and cone responses were recorded. Vision declined progressively, with rod and cone ERG responses undetectable in patients >20 years. Phenotype data of a total of 7 patients (6–69 years) from three large consanguineous families, all carrying a p.Y226C founder mutation, offer a unique view into the progressive nature of the disorder in psychophysical testing, morphology, and rod and cone ERG.
RDH12 loss–of–function results in a characteristic form of early–onset and progressive rod–cone degeneration, irrespective of the type of mutations present. The clinical course appears to be similar to – yet clearly distinguishable from – that of patients with RPE65 mutations, also affecting the visual cycle, especially with respect to visual acuity and visual fields at young age that are better preserved in patients with RDH12 mutations. From our data, it seems likely that various clinical designations appropriately describe the diagnosis in patients with RDH12 mutations, including early–onset or childhood–onset retinitis pigmentosa, or Leber congenital amaurosis type II. The identification and characterization of patients harbouring RDH12 mutations may be important for future therapeutic trials.
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