Molecular Characteristics for Families

Different types of mutations have been reported in homozygosity or compound heterozygous.

DEGS1-related leukodystrophy is a genetic disorder due to mutations in DEGS1. The disease is inherited in an autosomal recessive manner: this means that both copies of the DEGS1 gene must be mutated in an individual to be affected, whereas heterozygotes (with only one mutated copy) are asymptomatic carriers and thus do not manifest the condition but are at risk of transmitting it. Parents of a patient are usually carriers of the mutations and they have a 25% chance to have other children affected. Therefore, a genetic counselling and testing at risk family members are crucial for these families.

Lipid desaturase DEGS1 converts dihydroceramide (DhCer) into ceramide (Cer) in the final step of the de novo biosynthesis pathway. DhCer/Cer imbalance disturbs the exquisitely regulated process of myelin sheath biogenesis and compaction. Accumulation of DhCer is involved in many stress signals such as cell cycle regulation.
This suggests a critical role of DEGS1 and Cer metabolism in myelin development and maintenance, but also in neuronal/ axonal functioning.