From the clinic to the research laboratory. The role of the clinician in molecular genetic studies.

BACKGROUND

The first physician to examine a patient with a genetic disorder or birth defect is usually a specialist in a field other than genetics. The presentation of certain categories of patients of particular interest to molecular genetics research may be distinct. The recognition of these patients by clinicians is fundamental to the study of genetic disorders at the DNA level.

OBSERVATIONS

Neurofibromatosis type 1 is a paradigm for how the study of a single genetic disease and its multiple molecular features has been facilitated by the use of various categories of patients. Other examples of interest to dermatologists, surgeons, and other specialists are discussed to demonstrate how the identification of key patients was instrumental in studies of gene localization and subsequent cloning, gene clusters or contiguous gene deletion syndromes, or mutation phenomena such as imprinting, uniparental disomy, and gonadal mosaicism. The molecular researcher has limited access to surgical specimens, and the donation of skin, tumor, and other tissues may lead to increased knowledge of new mutations in somatic mosaicism, or loss of heterozygosity of tumor suppression genes in cancer.

CONCLUSIONS

Guidelines are suggested to alert the physician to each of these categories of individuals with unusual presentation, as well as to recognize that the study of families with rare disorders may enable scientists to locate the responsible genes. The teamwork of clinician and molecular researcher is essential for the advancement of our understanding of DNA mechanisms in genetic disease. The ethics involved in referral of patients to molecular genetic research studies are discussed.