Research Project
Full description Leukodystrophies are inherited diseases that result from the pathological reduction of myelin, the dielectric material that insulates axons in the human brain. Children suffering from a leukodystrophy have substantial morbidity and mortality, with more than a third dying by age eight. Unfortunately, despite the fact that the incidence of these diseases is relatively high (at least 1 in 7,000 births), more than half of all leukodystrophy patients are never fully diagnosed - i.e. the inherited mutation at the root of their affliction remains unknown. In this research project, we are harnessing the power of next generation sequencing technology to identify novel gene variants that cause leukodystrophy, the first step required to develop treatments for this disease. To achieve this, we are currently in the process of sequencing the genomes and/or exomes (i.e. the subset of the genome that contains protein coding genes) of approximately 300 children affected by these illnesses and, where possible, their unaffected family members. In total we will be sequencing the exomes of more than 1000 individuals. In the pilot phase of this project, we have identified the genetic basis of two novel types of leukodystrophy. These two discoveries were reported as back-to-back publications in the high-ranking American Journal of Human Genetics in April 2013. These cases have been of significant public interest and gained substantial media attention. Indeed, it is one of the first to show that by interrogating the genomes of previously "undiagnosable" children, we can not only uncover the cause of their illness, but in the process identify entirely new diseases. We have every expectation that our follow-on cohort study will be similarly successful.