Ceramide synthase TLCD3B is a novel gene associated with human recessive retinal dystrophy.
TLCD3B
ceramide synthase
cone–rod degeneration
novel disease gene
retinal degeneration
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
20
05
2020
accepted:
30
09
2020
revised:
29
09
2020
pubmed:
21
10
2020
medline:
4
6
2021
entrez:
20
10
2020
Statut:
ppublish
Résumé
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. 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. 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 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.
Identifiants
pubmed: 33077892
doi: 10.1038/s41436-020-01003-x
pii: S1098-3600(21)04943-1
pmc: PMC7936949
mid: NIHMS1645491
doi:
Substances chimiques
Oxidoreductases
EC 1.-
dihydroceramide desaturase
EC 1.3.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
488-497Subventions
Organisme : NIH HHS
ID : 1S10RR026550
Pays : United States
Organisme : NIH HHS
ID : S10 OD023469
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY022356
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY002520
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY018571
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
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