Triplication of SHOX gene in a boy with short stature.

The assessment that heterozygous SHOX mutations leading to SHOX haploinsufficiency play a role in subjects with idiopathic short stature (ISS) is already documented in literature as well as the suggestion that additional copies of SHOX are strongly implicated in a condition of tall stature. However, we report the first case of short stature in a male associated with the presence of 3 copies of SHOX gene.Through a chromosome analysis, using Multiplex Ligation-dependent Probe Amplification method of SHOX salsa P018B kit and microsatellites analysis, we identify a new interstitial isolated duplication of the SHOX gene and its enhancer caused by a larger duplication of PAR1 region in a ISS boy. Consequently, we form the hypothesis that this chromosome re-arrangement disrupts the regular interaction between enhancer and promoter, resulting in a transcription block and determining a lack of gene activation and causes the clinical feature of short stature.