SHOX at a glance: from gene to protein

Abstract

The Short Stature Homeobox-containing Gene SHOX was identified as the genetic cause of the short stature phenotype in patients with Turner Syndrome and in certain patients with idiopathic short stature. Shortly after, SHOX mutations were also associated with the growth failure and skeletal deformities seen in patients with Léri - Weill dyschondrosteosis and Langer mesomelic dysplasia. Today it is estimated that SHOX mutations occur with an incidence of roughly 1:1,000 in newborns, making mutations of this gene one of the most common genetic defects leading to growth failure in humans. This review summarises the involvement of SHOX in several short stature syndromes and describes recent advances in our understanding of SHOX functions and regulation. We also discuss the current evidence in the literature that points to a role of this protein in growth and bone development. These studies have improved our knowledge of the SHOX gene and protein functions, and have given insight into the etiopathogenesis of short stature. However, the exact role of SHOX in bone development still remains elusive and poses the next major challenge for researchers in this field.