SHOX: pseudoautosomal homeobox containing gene for short stature and dyschondrosteosis.

A growth gene has been postulated, on the basis of genotype-phenotype correlations in patients with sex chromosome aberrations, to exist on the short-arm pseudoautosomal region (PAR1) of the sex chromosomes. Recently, Rao et al. have identified a novel homeobox containing gene, SHOX (short stature homeobox containing gene), from the distal part of PAR1, by means of a positional cloning method. SHOX is most strongly expressed in bone marrow fibroblasts, implying that SHOX plays a positive role in bone growth and development. In addition, SHOX is expressed from an inactive X chromosome, as well as an active X and a normal Y chromosome, suggesting that SHOX escapes X-inactivation and exerts the dosage effect in sex chromosome aberrations. Mutational analysis of SHOX was done in about 400 patients with idiopathic short stature, identifying three types of heterozygous nonsense and missense mutations. Furthermore, fluorescence in situ hybridization analysis of SHOX was performed in six Japanese families with dyschondrosteosis, demonstrating microdeletions involving SHOX in all the patients. The results indicate that SHOX is responsible for short stature and dyschondrosteosis.