Glypicans are a family of glycosylphosphatidylinositol (GPI)-anchored, 
membrane-bound heparan sulfate (HS) proteoglycans. Their biological roles are 
only partly understood, although it is assumed that they modulate the activity 
of HS-binding growth factors. The involvement of glypicans in developmental 
morphogenesis and growth regulation has been highlighted by Drosophila mutants 
and by a human overgrowth syndrome with multiple malformations caused by 
glypican 3 mutations (Simpson-Golabi-Behmel syndrome). We now report that 
autosomal-recessive omodysplasia, a genetic condition characterized by 
short-limbed short stature, craniofacial dysmorphism, and variable developmental 
delay, maps to chromosome 13 (13q31.1-q32.2) and is caused by point mutations or 
by larger genomic rearrangements in glypican 6 (GPC6). All mutations cause 
truncation of the GPC6 protein and abolish both the HS-binding site and the 
GPI-bearing membrane-associated domain, and thus loss of function is predicted. 
Expression studies in microdissected mouse growth plate revealed expression of 
Gpc6 in proliferative chondrocytes. Thus, GPC6 seems to have a previously 
unsuspected role in endochondral ossification and skeletal growth, and its 
functional abrogation results in a short-limb phenotype.