This report describes leukodystrophy, hypomyelinating, 18 (HLD18); HLD18 exhibits autosomal recessive inheritance. The human gene implicated in this disease is DEGS1, the primary dihydroceramide desaturase gene in human. There is a single orthologous gene in Drosophila, designated ifc.
Several UAS constructs of the wild-type human Hsap\DEGS1 gene have been introduced into flies; heterologous rescue (functional complementation) of the amorphic ifc larval lethal phenotype has been demonstrated.
For related work in Drosophila, see the human disease model report 'activity-dependent neurodegeneration, DEGS-related' (FBhh0001142).
[updated Nov. 2019 by FlyBase; FBrf0222196]
Hypomyelinating leukodystrophies constitute a subset of genetic white matter disorders characterized by substantial and permanent deficits in CNS myelin deposition. Most patients with severe hypomyelination present in infancy or early childhood and develop severe neurological deficits; clinical presentation can also be mild with onset of symptoms in adolescence or adulthood (Wolf et al., 2021; pubmed:33324001).
[LEUKODYSTROPHY, HYPOMYELINATING, 18; HLD18](https://omim.org/entry/618404)
[DELTA(4)-DESATURASE, SPHINGOLIPID, 1; DEGS1](https://omim.org/entry/615843)
Hypomyelinating leukodystrophy-18 (HLD18) is an autosomal recessive neurologic disorder characterized by onset of global developmental delay usually in early infancy. Affected individuals have very poor psychomotor development, including inability to sit or walk independently in the more severe cases, as well as poor or absent speech, dystonia, and spasticity. A subset of patients may develop seizures. Brain imaging shows hypomyelinating leukodystrophy affecting various brain regions; some patients may also have progressive atrophy of the corpus callosum, thalami, and cerebellum (summary by Pant et al., 2019; pubmed:30620337). [from MIM:618404; 2019.11.07]
Hypomyelinating leukodystrophy-18 (HLD18) is caused by homozygous or compound heterozygous mutation in the DEGS1 gene. [from MIM:618404; 2019.11.07]
DEGS1 encodes a member of the membrane fatty acid desaturase family which is responsible for inserting double bonds into specific positions in fatty acids. It is predicted to be a multiple membrane-spanning protein localized to the endoplasmic reticulum. [Gene Cards DEGS1; 2019.11.07]
The DEGS1 enzyme converts the sphingolipid dihydroceramide into ceramide in the final step of the de novo biosynthesis pathway (Pant et al, 2019; pubmed:30620337).
Many to one: 2 human to 1 Drosophila. The two human genes are DEGS1 and DEGS2.
