Distilled database identifies genetic links to rare diseases
24 March 2023
Published online 4 November 2013
Gangliosides are membrane lipids found mostly in the brain and help facilitate cell-to-cell communication between neurons. A deficiency gives rise to a large group of inherited disorders, the lysosomal storage diseases.
Researchers from the UK, Canada, the United States and Kuwait collected and analyzed DNA and RNA samples from three unrelated families living in Kuwait, Italy and the Old Order Amish with a complex form of hereditary motor neuron disorder known as spastic paraplegia, which lead to progressive stiffness and contraction in the lower limbs.
They found mutations in the gene B4GALNT1 that codes for GM2 synthase enzyme, which catalyses the second step in the biosynthesis of complex ganglioside, publishing their findings in Brain.
The mutation resulted in non-functional GM2 synthase enzyme, leading to a deficiency in the lipid. This lack of ganglioside caused nerve degeneration and led to impaired motor coordination. Biochemical analysis of the collected samples confirmed a lack of GM2 and an increase in its precursor, GM3.
"The study has identified a new cause of a neurodegenerative disease, complex spastic paraplegia. It is possible to carry out both genetic and biochemical tests in families suspected to have such disease for the diagnosis," says Andrew Crosby, a senior author of the study.