SHOX variations in Idiopathic Short Stature in North India and its overall prevalence in Asia

Abstract

Abstract Background Short stature homeobox (SHOX) haploinsufficiency underlies idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD). The worldwide prevalence of SHOX variations in ISS varies from 2.5–15%. This study aims to assess the implication of SHOX variation in ISS in North India and its overall prevalence in Asian population. Methods SHOX gene analysis carried out by Multiplex ligation dependent probe amplification (MLPA) followed by Sanger sequencing in 54 patients with variable phenotypes. Meta-analysis was done to evaluate its prevalence which comprises 11 previous studies including present, carried out on a total of 979 participants. Results SHOX gene analysis resulted in 12.9% of positivity (7.4% deletions and 5.5% duplications). SHOX association was seen significantly related to gender, with predominance in female sex (P-value: 0.047). Short arms and forearms were the only significantly associated trait seen in 51.85% of children. We have found a rare association of multiple exostosis with LWD in a child with deletion. The prevalence of SHOX variation came as 15.2% in Asians. No significant difference was found in geographical region-specific analysis. Conclusion This meta-analysis compiles findings from the last decade and provides an updated picture of the prevalence of SHOX variations in Asians, emphasizing their potential as therapeutic targets in ISS patients.