This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.A large number of inherited and acquired disorders can affect the function of the adrenal cortex, causing either reduced (hypo) or increased (hyper) adrenocortical function. Our team has focused on elucidating the biochemical defects and the molecular genetic basis of disorders of steroidogenesis, primarily in Congenital Adrenal Hyperplasia. Over the past 50 years, we have studied extensively the clinical, hormonal and molecular genetic basis of these disorders, identifying the defect within the steroid synthesis pathway which causes the disease and establishing a treatment which specifically targets the enzyme defect. This can be straightforward in cases where the genetic mutations causing a disease have been characterized (eg 21-hydroxylase deficiency, accounting for 90-95% of all CAH cases) and the mechanism of disease is known; however, this can be particularly difficult in cases where the determinant gene has not yet been identified and the mechanism of disease remains unknown. Therefore the following protocol outlines the means by which we are able to characterize the diverse clinical spectra of patients with rare steroidogenesic enzyme defects and their family members.Hypothesis related to CAH:1. Genotype predicts phenotype in patients with salt wasting, simple virilizing, and the non-classical forms of congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency.2. There are examples of non-concordance of genotype to phenotype, particularly with regard to the salient feature of salt-wasting, which merit investigation.
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