The phenotype of early-onset retinal degeneration in persons with RDH12 mutations.
OBJECTIVE
To describe the retinal dystrophy phenotype associated with mutations in RDH12, the gene encoding a retinoid dehydrogenase/reductase expressed in the photoreceptor cells.


METHODS
Sixteen persons from 12 families with pathogenic RDH12 mutations on both alleles were studied. Retinal phenotypes were characterized by ophthalmic examination, including psychophysical and standardized electrophysiological methods and multifocal electroretinography (mfERG).


RESULTS
The retinal disease in persons with RDH12 mutations in the homozygous (p.G127X, p.Q189X, p.Y226C, p.A269GfsX1, and p.L274P) or compound heterozygous state (p.R65X/p.A269GfsX1, p.H151D/p.T155I, p.H151D/p.A269GfsX1) was diagnosed initially as Leber congenital amaurosis (LCA) or early-onset retinitis pigmentosa. These individuals appeared to share a common clinical picture, independent of the type of mutation, characterized by poor, yet useful visual function in early life, followed by progressive decline due to both rod and cone degeneration. Marked pigmentary retinopathy, including bone spicules in the peripheral retina, was present in all persons older than age 6, and pronounced maculopathy was evident in persons older than 7 years. A unique view into the progressive nature of the disorder was achieved by evaluation of seven affected persons from three consanguineous families, all carrying the homozygous p.Y226C mutation.


CONCLUSIONS
Ophthalmic findings in persons with RDH12 mutations suggest that RDH12 loss-of-function results in a characteristic form of early and progressive rod-cone degeneration distinct from that caused by mutations in other LCA genes. From our data, it seems likely that various clinical designations appropriately describe the diagnosis in these persons, including early-onset retinitis pigmentosa, LCA type II, and childhood retinal dystrophy.
Schuster
Andreas
A
Department of Pathophysiology of Vision and Neuroophthalmology, University Eye Hospital, Schleichstrasse 12-16, D-72076 Tübingen, Germany.
Janecke
Andreas R
AR
Wilke
Robert
R
Schmid
Eduard
E
Thompson
Debra A
DA
Utermann
Gerd
G
Wissinger
Bernd
B
Zrenner
Eberhart
E
Gal
Andreas
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003118:Color Perception; D004596:Electroretinography; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics*; D014792:Visual Acuity; D014794:Visual Fields
D000429:Alcohol Oxidoreductases; C489649:RDH12 protein, human