Publication Date
3-1-2021
Journal
Genetics in Medicine
DOI
10.1038/s41436-020-01003-x
PMID
33077892
PMCID
PMC7936949
PubMedCentral® Posted Date
4-20-2021
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Animals, Electroretinography, Humans, Mice, Oxidoreductases, Retina, Retinal Cone Photoreceptor Cells, Retinal Degeneration, Retinal Dystrophies, Retinal degeneration, ceramide synthase, cone-rod degeneration, novel disease gene, TLCD3B
Abstract
PURPOSE: Previous studies suggest that ceramide is a proapoptotic lipid as high levels of ceramides can lead to apoptosis of neuronal cells, including photoreceptors. However, no pathogenic variant in ceramide synthases has been identified in human patients and knockout of various ceramide synthases in mice has not led to photoreceptor degeneration.
METHODS: Exome sequencing was used to identify candidate disease genes in patients with vision loss as confirmed by standard evaluation methods, including electroretinography (ERG) and optical coherence tomography. The vision loss phenotype in mice was evaluated by ERG and histological analyses.
RESULTS: Here we have identified four patients with cone-rod dystrophy or maculopathy from three families carrying pathogenic variants in TLCD3B. Consistent with the phenotype observed in patients, the Tlcd3b
CONCLUSION: Our results provide a link between loss-of-function variants in a ceramide synthase gene and human retinal dystrophy. Establishment of the Tlcd3b knockout murine model, an in vivo photoreceptor cell degeneration model due to loss of a ceramide synthase, will provide a unique opportunity in probing the role of ceramide in survival and function of photoreceptor cells.
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Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Medical Sciences Commons, Medical Specialties Commons
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