Short stature homeobox-containing gene duplications in 3.7% of girls with tall stature and normal karyotypes

Aim The short stature homeobox containing gene (SHOX) plays an important role in short stature, but has not been explored in detail in a tall stature population before. This study explored the prevalence of SHOX aberrations in girls diagnosed with idiopathic tall stature with a normal karyotype. Methods We studied SHOX aberrations in 81 girls with a median age of 10.43 (7.17-12.73) years diagnosed with tall stature who were referred to our clinic at Copenhagen University Hospital, Denmark, between 2003-2013. SHOX copy variations were analysed by quantitative polymerase chain reaction and aberrations were confirmed by multiplex ligation probe-dependent amplification. Results One extra SHOX copy was found in three (3.7%) of the 81 girls with tall stature and their heights were 2.87, 3.71 and 3.98 standard deviation scores (SDS) above the median height SDS of the girls with two SHOX copies. Their sitting height / height ratios (-3.08, -2.00 and -2.18 SDS) were all lower than the populationmean. Despite these SHOX duplications, the three girls were clinically and biochemically comparable to the 78 girls with two SHOX copies. Conclusions This study was the first to demonstrate SHOX duplications in three girls with tall stature and normal karyotypes. This article is protected by copyright. All rights reserved.