Frameshift, nonsense and missense mutations have been reported in homozygosity or compound heterozygous. Patients with homozygous loss-of-function mutations tended to have a more severe course, although some patients with missense mutations also had a severe disease course.
Lipid desaturase DEGS1 converts dihydroceramide (DhCer) into ceramide (Cer) in the final step of the de novo biosynthesis pathway. Accumulation of DhCer is involved in many stress signals such as cell cycle regulation, autophagy induction, apoptosis, and ROS generation. DhCer/Cer imbalance on the cellular membranes disturbs the exquisitely regulated process of myelin sheath biogenesis and compaction, including the lipid-lipid and lipid-protein interactions. Disruption of DEGS1 also likely results in a broader imbalance of overall sphingolipid metabolism, which has structural and signaling functions.
This suggests a critical role of DEGS1 and Cer metabolism in myelin development and maintenance, but also in neuronal/ axonal functioning.
DEGS1