The role of clinical pharmacology in molecular genetics.

PROBLEM: Discovering the causes of unusual phenotypes in human subjects is an important aspect of patient-oriented research.

MATERIAL: The tools of clinical pharmacology are uniquely useful in addressing these problems. PATIENTS, SUBJECTS, OR CASE HISTORIES: We evaluated a 42-year-old patient with lifelong orthostatic hypotension and ptosis of the eyelids. He underwent a series of biochemical, physiological, and pharmacological tests outlined in this article.

RESULTS

These studies indicated that sympathetic innervation was intact but that the sympathetic neurotransmitter was dopamine rather than norepinephrine. These results demonstrated that dopamine-beta-hydroxylase deficiency underlies the clinical abnormalities of this patient.

CONCLUSION

In selected individuals with unusual phenotypes, the techniques of clinical chemistry and clinical pharmacology can define the nature of the defect at almost the resolution of the human genome.