What the future holds for the genetic diagnosis for neurodegeneration with brain iron accumulation syndromes?

Abstract

We have recently seen a tremendous revolutionary development in molecular sciences with emerging genetic and genomic technologies. This has shed light on rare inherited disorders including Neurodegeneration with Brain Iron Accumulation (NBIA), a heterogeneous group of neurological disorders caused by excessive iron deposition in the brain. Despite this, a large proportion of cases cannot yet be explained by mutations in any of the known genes. However, new NBIA genes will continue to be described and strategic work-up in large patient cohorts may also unravel potential genetic and epigenetic factors influencing or determining the clinical and radiological presentation of individuals with NBIA. It is tantalizing to imagine how far platforms for transcriptome analysis and genomic profiling, such as genome-wide microRNA assays and methylation studies, and metabolomics, will also shed further light on NBIA syndromes. In turn, improved understanding may lead to novel approaches to modify the course of illness by identifying therapeutic targets that have already been validated in other relevant human disease models as well as aiding the development of potential new neuroprotective compounds. These and other timely issues of NBIA disorders are discussed in this editorial.