Peripapillary sparing in RDH12-associated Leber congenital amaurosis
Open accessAbstract
BACKGROUND: Peripapillary sparing is a characteristic that is traditionally described as pathognomonic for Stargardt disease. MATERIALS AND METHODS: We present a multimodal assessment of four Leber congenital amaurosis (LCA) cases with congenital macular atrophy and severely attenuated electroretinogram findings caused by bilallelic mutations in RDH12. RESULTS: Fundus autofluorescence imaging revealed a general loss of retinal pigment epithelium across the macula except for the peripapillary region in both eyes of all patients. Spectral domain-optical coherence tomography confirmed relative preservation in this area along with retinal thinning and excavation throughout the rest of the macula. LCA was diagnosed based on clinical exam and retinal imaging, and subsequently confirmed with genetic testing. CONCLUSIONS: Peripapillary sparing is a novel phenotypic feature of RDH12-associated LCA.
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Pathogenic variants in RDH12 cause autosomal recessive LCA and EOSRD (LCA13), characterized by severe progressive rod-cone dystrophy with widespread RPE atrophy, bone-spicule pigmentation, vascular attenuation, macular atrophy, and corresponding macular excavation.
“Pathogenic variants in RDH12 have been shown to cause autosomal recessive LCA and EOSRD (LCA13, OMIM #612712), characterized by severe progressive rod-cone dystrophy with widespread RPE atrophy, bone-spicule pigmentation, vascular attenuation, macular atrophy and corresponding macular excavation [113,149,151,152].”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [149]
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Experimental — accuracy not yet measuredRDH8 contributes approximately 70% and RDH12 approximately 30% of all-trans-RDH activity.
“RDH8 contributes to approximately 70% and RDH12 to approximately 30% of all-trans-RDH activity.”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [149]
The Discussion describes RDH12’s role in the visual cycle but gives no share of all-trans-RDH activity. Searches for RDH8 and the 70%/30% activity split found no passage addressing the claimed proportions; the Discussion’s separate 30% figure concerns patients’ preferred retinal locus, not enzyme activity. Page numbers were not available in our copy. (LLM, conf=0.76)
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- Authors
- Garg, A., Lee, W., Sengillo, J. D., Allikmets, R., Garg, K., & Tsang, S. H.
- Affiliations
- Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
- Columbia University Irving Medical Center (US)
- SUNY Downstate Health Sciences University (US)
- Columbia University (US)
- Corresponding author
- Tsang, Stephen H.
- Venue
- Ophthalmic Genetics
- Publisher
- Informa UK Limited
- Published
- 2017-05-17
- Volume
- 38
- Issue
- 6
- Pages
- 575-579
- ISSN
- 1381-6810 (ISSN-L)
- 1744-5094
- PMC
- PMC6314194
- OpenAlex
- W2614258012
- Cited by
- 27
- References
- 18
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 3 · 2014: 1
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Ophthalmic Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5P30EY019007, R01EY018213, R01EY024698, R01EY026682, R21AG050437)
- Research to Prevent Blindness (RPB) Physician-Scientist Award, unrestricted funds from RPB, RPB medical student research fellowship (N/A)
- Schneeweiss Stem Cell Fund (N/A)
- National Cancer Institute Core (5P30CA013696)
- Tistou and Charlotte Kerstan Foundation (N/A)
- Crowley Family Fund (N/A)
- Foundation Fighting Blindness (C-NY05-0705-0312)
- New York State (C029572)
- Gebroe Family Foundation (N/A)
- RD-CURE Consortium (N/A)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- Leber congenital amaurosis, RDH12, retinal pigment epithelium, macular atrophy, fundus autofluorescence, optical coherence tomography, electroretinogram, phenotypic traits, genotype-phenotype correlation
- MeSH terms
- Adolescent, Alcohol Oxidoreductases, Atrophy, Child, DNA Mutational Analysis, Electroretinography, Female, Genetic Testing, Genotype, Humans, Male, Mutation, Optic Disk, Pedigree, Tomography, Optical Coherence, Retinal Pigment Epithelium, Young Adult, Leber Congenital Amaurosis, Multimodal Imaging
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