Genetics

Abstract

With a few exceptions, rheumatic diseases are similar to many other common medical conditions in that they are genetically complex, with a multifactorial etiology. Simple Mendelian disorders (autosomal dominant, recessive, or sex linked) are encountered relatively infrequently in rheumatologic practice, although some exciting successes in this area (notably the cloning of the gene for familial Mediterranean fever; see ref. 1) may ultimately lead to new approaches to the general problem of inflammation. It is clearly important for the rheumatologist to be aware of the Mendelian diseases that can rarely underlie common rheumatologic conditions such as gout (e.g., PP-ribose-P synthetase overactivity or hypoxanthine guanine phosphoribosyltransferase (HGPRT) deficiency). Beyond this, the problem of genetics in rheumatic disease may strike the newcomer as dauntingly complicated and of limited utility. The purpose of this chapter is to provide the tools to approach this topic with confidence. It will be necessary for the educated rheumatologist to have some ability to interpret the wealth of genetic information that is likely to emerge over the next few years because of the completion of the Human Genome Project (2) and the application of genetic mapping techniques to the major rheumatic diseases.