The development of high throughput sequencing (Next Generation Sequencing, NGS) in the 2000s marked a major turning point in genome studies. Exome technology makes it possible to sequence all exons in the genome. The exon is the part of the gene that is translated into proteins. Leukodystrophies are a group of genetic diseases that affect white matter and primarily its major component, myelin. Despite advances in gene identification, 60% of patients remain without any genetic abnormalities found. We performed exome sequencing in a cohort of 80 patients with leukodystrophies of undetermined cause.

We have identified the causal mutation in 56% of cases, the remaining 44% are being analyzed with several candidate variants. This analysis allowed us to divide our cohort into three subgroups. A group with mutations in known genes for leukodystrophies (15%), a 2nd group with mutations in genes already involved in another genetic disease and with a very atypical clinical picture (9%), and a 3rd group with mutations in potentially candidate genes (32%).

The identification of mutations in known leukodystrophy genes by exome sequencing has demonstrated the major interest in developing a chip that brings together all known leukodystrophy genes for diagnostic application.