Turner syndrome (TS) is a sporadic disorder affecting ~ 1/2500 live female births. It is caused by the absence of all or significant parts of one sex-chromosome. Major developmental consequences include severe short stature, ovarian failure and distinctive cognitive and behavioral traits, with renal and cardiovascular defects affecting a minority. Adults with TS have excessive rates of osteoporosis, hypertension and diabetes mellitus and experience morbidity and mortality several-fold higher than the general population. Many of the problems of TS result from haplo-insufficiency for X-chromosome encoded genes, most of which remain unknown. Previous studies attempting to correlate genotype with phenotype in TS have been limited due to small numbers of subjects, limited genetic methodology and incomplete phenotypic characterization. This study aims to correlate TS phenotypes and genotypes using advanced clinical and genetic diagnostic methodologies, with the goal of identifying X-chromosome genes and epigenetic mechanisms causing the different features of TS. For TS subjects with a 45X genotype, the parental origin of the single normal X-chromosome will be traced to identify genomically imprinted features of the disorder. X chromosomal structural defects will be analyzed using high-resolution physical mapping in relation to emerging sequence data from the Human Genome Project. The elucidation of genetic mechanisms in TS will help improve the diagnosis and treatment of girls and women with this disorder and will further our understanding of gene dosage effects in general.