Gaucher disease: insights from a rare Mendelian disorder.

It is becoming quite evident that studies of Mendelian disorders can provide important insights into common neurologic disorders. These rare inherited disorders often offer a unique window into seemingly unrelated diseases. The number of studies focusing on genetic contributions to neurologic disorders is growing exponentially. When undertaking the challenges associated with identifying the genes underlying complex neurological disorders, it is valuable to consider lessons gleaned from decades of studies of rare Mendelian disorders. This review will focus on lessons learned and challenges encountered in the study of one such monogenic disorder, Gaucher disease, focusing both on purely clinical observations, as well as the impact of such insights on understanding more common complex diseases. Studies of patients with Gaucher disease have led to unanticipated research directions impacting several distinct medical disciplines. Some notable examples include the link between mutations in the glucocerebrosidase gene and the development of Parkinson disease and related Lewy body disorders, elucidation of the role of glucocerebrosidase in skin barrier function and neonatal viability, and the connection between lysosomal transport and myoclonic epilepsy.