J Clin Res Pediatr Endocrinol. 2024; 16(1): 41-49 | DOI: 10.4274/jcrpe.galenos.2023.2023-3-13

SHOX Variations in Idiopathic Short Stature in North India and a Review of Cases from Asian Countries

Priyanka Srivastava¹, Ankita Tyagi¹, Chitra Bamba¹, Anu Kumari¹, Harvinder Kaur², Saurabh Seth¹, Anupriya Kaur¹, Inusha Panigrahi¹, Devi Dayal³, Subhodip Pramanik⁴, Kausik Mandal^5
1Advanced Pediatrics Centre (APC), Postgraduate Institute of Medical Education & Research (PGIMER), Genetic Metabolic Unit, Chandigarh, India
²Advanced Pediatrics Centre (APC), Postgraduate Institute of Medical Education & Research (PGIMER), Child Growth and Anthropology Unit, Chandigarh, India
³Advanced Pediatrics Centre, Postgraduate Institute of Medical Education & Research (PGIMER), Pediatric Endocrinology Unit, Chandigarh, India
⁴IPGMER and SSKM Hospital, Clinic of Endocrinology, Kolkata, India
⁵Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Department of Medical Genetics, Lucknow, India

INTRODUCTION: Short stature homeobox (SHOX) haploinsufficiency underlies idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis. The worldwide prevalence of SHOX variations in ISS varies from 2.5% to 15.0%. The aim of this study was to assess the implication of SHOX variation in ISS in North Indians and compare this with other cases of SHOX variations from Asian population.
METHODS: SHOX gene analysis was carried out by multiplex ligation-dependent probe amplification followed by Sanger sequencing in 54 patients with variable phenotypes. Comparison with other reports in a meta-analysis comprising the current study and 11 previous studies (n=979) was performed.
RESULTS: SHOX analysis resulted in 12.9% positivity (7.4% deletions and 5.5% duplications). SHOX association was seen significantly related to gender, with predominance in females (p=0.047). Short arms and forearms were the only significantly associated trait seen in 51.9% of children. The overall prevalence of SHOX variation was 15.2% in Asians with ISS. No significant difference was found in geographical region-specific analysis.
DISCUSSION AND CONCLUSION: This study summarises 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. Further high quality, large investigations including functional validation is warranted to validate this association.

Keywords: Idiopathic short stature, SHOX, MLPA, Sanger sequencing, meta-analysis, prevalence

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