GENETIC-HETEROGENEITY IN MULTIPLE EPIPHYSEAL DYSPLASIA

Multiple epiphyseal dysplasia (MED) comprises a group of hereditary ch ondrodysplasias in which there are major anatomic abnormalities of the long tubular bones. The Fairbank and Ribbing types are the most frequ ently cited types of MED. They are primarily defined radiographically and are autosomal dominant conditions. Recently, MED in one family was shown to map to the pericentromeric region of chromosome 19 and is pr obably allelic to pseudoachondroplasia. We have tested linkage with si x short tandem repeat markers from chromosome 19 to autosomal dominant MED in one four-generation family and to MED in a unique family with three of seven siblings affected and with unaffected parents. Autosoma l dominant MED in family 1 was linked with a maximum LOD score, at D19 S212, of 3.22 at a recombination fraction (theta) of .00. Linkage to c hromosome 19 was excluded with MED in the other family, under both aut osomal recessive and autosomal dominant, with either reduced-penetranc e or germ line-mosaicism models. Linkage to candidate genes COL9A1, CO L9A2, and COL11A2 was tested and excluded for both genetic models in t his family. COL11A1 was excluded under a recessive model. We have conf irmed linkage of autosomal dominant Fairbank MED to chromosome 19 and have demonstrated that MED is genetically heterogeneous.