Ceramide Synthase TLCD3B Is a Novel Gene Associated With Human Recessive Retinal Dystrophy

Authors

Renae Elaine Bertrand
Jun Wang
Kaitlyn H Xiong
Chinthana Thangavel
Xinye Qian
Rola Ba-Abbad
Qingnan Liang
Renata T Simões
Shirley A M Sampaio
Keren J Carss
F Lucy Raymond
Anthony G Robson
Andrew R Webster
Gavin Arno
Fernanda Belga Ottoni Porto
Rui Chen

Language

English

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

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.

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

Published Open-Access

yes

Recommended Citation

Bertrand, Renae Elaine; Wang, Jun; Xiong, Kaitlyn H; et al., "Ceramide Synthase TLCD3B Is a Novel Gene Associated With Human Recessive Retinal Dystrophy" (2021). Faculty and Staff Publications. 409.
https://digitalcommons.library.tmc.edu/baylor_docs/409