Grant: Institute of Genetics Clinical Investigatorship Award

It has been 20 years since the official commencement of the Human Genome Project and six years since its completion and with the recent introduction of instruments capable of producing millions of DNA sequence reads in a single run there are now indications for renewed focus on understanding rare single-gene disorders. Of the 25,000 protein coding human genes only about 10% have been implicated in human disease; there remain at least 3,500 Mendelian phenotypes for which the molecular basis is unknown in addition to a vast number of single-gene disorders that have not yet been described. Many of these disorders have significant impact on the health of the nervous system and are associated with either abnormal neurodevelopment necessitating lifelong care and support or with neurodegeneration affecting previously well and productive children and adults with debilitating and often life-limiting disease. Subspecialty genetics clinics are enriched for rare and unreported phenotypes, providing resources for the identification of new genes and pathways associated with novel human disease. The goal of this research is to identify genes for novel neurological disorders and understand the role of these genes in disease pathogenesis; thereby providing pathways for potential therapeutic investigation. Importantly, the knowledge gained from this research will be translated to patients through increased phenotypic understanding and access to diagnostic testing.