MOSAICISM IN PSEUDOACHONDROPLASIA

Pseudoachondroplasia (PSACH) is a spondylo-epi-metaphyseal dysplasia c haracterized by disproportionate short stature, generalized ligamentou s laxity, and precocious osteoarthritis. PSACH is caused by mutations in the cartilage oligomeric matrix protein (COMP) gene, which codes fo r a noncollagenous protein expressed in the territorial matrix of chon drocytes. Autosomal dominant inheritance has been demonstrated in many families; however, autosomal recessive inheritance has been suggested in some severe familial cases, Alternatively, germline/somatic mosaic ism has been proposed and is credible, since it has been shown that do minantly inherited and sporadic cases of PSACH are caused by the same genetic defect, Here, we present evidence demonstrating somatic mosaic ism in two PSACH families that were originally considered to represent autosomal recessive inheritance, The results of this study suggest th at autosomal recessive inheritance is unlikely and all cases of PSACH should be studied for mutations in COMP. (C) 1997 Wiley-Liss, Inc.