Identification of nine novel mutations in cartilage oligomeric matrix protein in patients with pseudoachondroplasia and multiple epiphyseal dysplasia

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1) are a llelic disorders caused by mutations in the gene encoding cartilage oligome ric matrix protein (COMP), PSACH is a dominant condition characterized by d isproportionate short stature; joint laxity, and early-onset osteoarthritis . EDM1 is a less severe skeletal dysplasia associated with average to mild short stature, joint pain, and early-onset osteoarthritis, COMP is an extra cellular matrix protein present in cartilage, ligament, and tendon tissues. Here, we report on nine novel mutations in COMP causing PSACH and EDM1, Fo ur of these mutations are in exons 13C and 14 where no previous mutations h ad been reported. One of those mutations was identified in two separate EDM 1 families. In addition, we have identified the first case of PSACH resulti ng from an expansion of the five aspartates in exon 17B, We are also report ing a mutation in a third PSACH family with somatic/germline mosaicism, The refore, this report increases the range of mutations that cause PSACH and E DM1 and provides additional regions to target for mutational analysis. (C) 1999 Wiley-Liss, Inc.