Current status of the human malformation map.

Abstract

The recent advances in recombinant DNA technology are now being applied to map and clone the genes for dysmorphic syndromes. The genes for almost 40% of the malformation and dysplasia syndromes listed in Smith's Recognizable Patterns of Human Malformation [Jones, 1988] have now been mapped and/or identified. This strategy has dramatically changed the way in which clinical geneticists look at the basic mechanisms of genetic disorders. The primary purpose of applying positional cloning to human disease, including malformation syndromes, is to use the cloned gene to understand the basic pathogenesis of the disorder at hand. The importance of the application of knowledge of mouse models, to human molecular biology and the significance of the role of the clinician in documenting astute observations that assist in mapping cannot be overemphasized. Many of the successful outcomes in gene cloning in dysmorphic syndromes that have occurred thus far were clearly helped by the recognition of patients with chromosomal rearrangements. Collaboration of molecular biologists and clinical geneticists will clearly lead to the continued elucidation of the map location and cloned gene of many other disorders.