EP342: Clinical testing of SHOX gene for SHOX deficiency disorders

Abstract

Haploinsufficiency of the short stature homeobox-containing (SHOX) gene causes a range of disorders from the milder phenotype of isolated short stature to the more severe Leri-Weill dyschondrosteosis (LWD). The SHOX gene maps to the pseudoautosomal region of the sex chromosomes, allowing for pseudoautosomal inheritance. Pathogenic SHOX variants on one allele cause LWD and familial short stature, while pathogenic variants on both alleles cause Langer mesomelic dysplasia (LMD). Deletions and duplications of the SHOX coding region, or the enhancer element(s) upstream or downstream of SHOX gene are representative of 80-90% of SHOX disorders, while the rest of the patients were identified to have pathogenic sequence variants.