The homozygous deletion of the 3' enhancer of the SHOX gene causes Langer mesomelic dysplasia.

Defects in the transcriptional control not involving the coding sequence of genes have emerged as a cause of several diseases, including Leri-Weill Syndrome (LWS) and its homozygous form, Langer Mesomelic Dysplasia (LMD), both caused by the inactivation of the SHOX gene. In a consanguineous LWS couple, MLPA and microsatellite analysis showed an heterozygous deletion in the 3’ SHOX regulatory region in both. By analysing their previously aborted fetus affected by LMD with a typical phenotype, the same deletion was found in a homozygous form. This is the first report of a pure homozygous deletion in a regulatory region causing disease in humans.