ABSTRACT
Early in the nineteenth century, there lived a woman in Venezuela, in a stilt village on the shores of a large lake, with an outlet to the sea, Lake Maracaibo. She died of a then unknown, and what was to prove to be a comparatively rare, slowly developing, devastating and ultimately fatal neurological disease. More than two centuries later it would be shown to have genetic origins, and would be passed on to a Venezuelan kindred, as an abnormal autosomal-dominant allele, where the prevalence nowadays is extremely high. The lake, and surrounding villages, would become a natural genetic laboratory. The first cases may have occurred in early seventeenth-century Europe, and debate continues as to whether all present-day cases are direct descendants, a founder effect, or whether any new mutations have since occurred, or can occur. Be that as it may, the Lady of the Lake, who bore nine children, is thought either to have lived with an affected European, possibly a Portuguese sailor who found his way into this natural and pleasant retreat, or to be the daughter of a woman who had done so.
