Identification of the first recurrent PAR1 deletion in Léri-Weill dyschondrosteosis and idiopathic short stature reveals the presence of a novel SHOX enhancer

SHOX, is a gene implicated in human growth.  Defects in SHOX, or its regulatory regions have been observed in ~60% of Léri-Weill dyschondrosteosis (LWD) patients, a skeletal dysplasia, and in 2-5% of idiopathic short stature (ISS) patients.  In this study, we identified the first recurrent deletion within the SHOX regulatory region in these disorders, 19/124 LWD and 11/576 ISS. Using chicken and human cell models to examine the deleted sequence, we subsequently identified a novel regulatory element that activates SHOX expression. In the individuals with the deletion, the level of SHOX activity is hence reduced, thus, resulting in the clinical features exhibited in these patients. (By Karen Heath, PhD, http://jmg.bmj.com/content/49/7/442 )