THE ROLE OF CLINICAL-PHARMACOLOGY IN MOLECULAR-GENETICS

Problem: Discovering the causes of unusual phenotypes in human subject s is an important aspect of patient-oriented research. Material: The t ools of clinical pharmacology are uniquely useful in addressing these problems. Patients, subjects, or case histories: We evaluated a 42-yea r-old patient with lifelong orthostatic hypotension and ptosis of the eyelids. He underwent a series of biochemical, physiological, and phar macological tests outlined in this article, Results: These studies ind icated that sympathetic innervation was intact but that the sympatheti c neurotransmitter was dopamine rather than norepinephrine. These resu lts demonstrated that dopamine-beta-hydroxylase deficiency underlies t he clinical abnormalities of this patient. Conclusion: In selected ind ividuals with unusual phenotypes, the techniques of clinical chemistry and clinical pharmacology can define the nature of the defect at almo st the resolution of the human genome.