21 October 2020
Genetic map of neurodegenerative disorder gives clues to pathology
Published online 6 February 2014
Hereditary Spastic Paraplegia (HSP) is a group of hereditary neurodegenerative disorders that result from a loss of function in the corticospinal tract (CST), which conducts signals from the brain to the spinal cord, leading to progressive spasticity of the lower limbs.
An international team of researchers, led by Joseph Gleeson from the University of California in San Diego, including researchers from Egypt, Iran, Iraq, Jordan, Libya, Morocco, Qatar, Saudi Arabia and Turkey, successfully doubled the number of known genetic causes of autosomal-recessive HSP, publishing their findings in Science.
By mapping select portions of the genome of some 93 patients from 55 families displaying the disorder, the team identified genetic mutations in about 75% of cases, including 18 candidate genes that had have never before been linked to the disease. Using this information, the researchers were able to generate a map, the 'HSP-ome', which included both previously known and the newly discovered mutations.
This led the researchers to additional mutations and implicated a number of biological pathways associated in this disorder, including cellular transport, nucleotide metabolism, and synapse and axon development. HSP was also linked to other more common neurodegenerative disorders, such as Alzheimer's disease.
"This was a collaborative effort with outstanding physician-scientists in the Middle East from the outset," says Gleeson. "We are indebted to the patients and families that participated and hope that the work can lead to new treatments for this devastating disorder."
- Novarino, G. et al. Exome Sequencing Links Corticospinal Motor Neuron Disease to Common Neurodegenerative Disorders. Science (2014) doi:10.1126/science.1247363