Skeletal dysplasias detectable by DNA analysis

The emerging data of the last few years outlining the molecular basis of skeletal dysplasias has been instructive in several respects. The number of genetic loci involved appears to be much fewer than anticipated. This is offset by the identification of several instances where phenotypically distinct entities are found to be allelic variants. With respect to diagnosis by DNA, most of the conditions recognized have several different mutations described. Consequently, while mutation analysis may be possible in a given case, close liaison with the investigating laboratory is essential if optimal results are to be obtained. Achondroplasia is unusual in that there is a common mutation and the other mutations related to the phenotype appear to cluster to a few codons. This review highlights the relationship between phenotypes of skeletal malformation, their underlying loci and mutations. These mutations appear to mediate their phenotypic effects through a diverse range of genetic mechanisms.