D.I.1 Novel Neuromuscular Diseases

Abstract

The clinical heterogeneity of neuromuscular disorders is well-recognised by clinicians, pathologists and geneticists involved in this area. However, the extent of this heterogeneity had not been appreciated until recently, due largely to the limitations of techniques and the size of families available for gene identification studies. The recent availability of novel genetic techniques, which include targeted enrichment platforms followed by massive parallel sequencing, whole exome and whole genome sequencing, are dramatically and rapidly changing this scenario. This is leading to the identification of numerous novel genes. My own group, in collaborative work with the Sanger Unit in Cambridge has during the course of the last year identified several new genes involved in congenital muscular dystrophies, congenital myopathies and neurogenic conditions. I am aware of rapid progress from a number of colleagues and collaborators across the world. It is realistic to expect that we will at least double the number of genes involved in neuromuscular conditions in the next few years. This brings significant challenges for the field; firstly the necessity to clearly define the phenotype of patients affected by these newly recognised conditions; secondly the need to be involved in collaborative studies to access other patients affected by these often exceedingly rare conditions; another challenge is the demonstration of pathogenicity of putative mutations in novel genes. These challenges can be addressed by ensuring deep phenotyping of patients, access to international collaboration networks and biobanked material, and multidisciplinary collaborations to address pathogenicity of novel mutations. A bigger challenge will be related to the full understanding of the function of all these novel genes, although the full ascertainment of mutations in different portions of a similar pathway, in conditions sharing similar clinic-pathological features, should provide important clues.