A novel point mutation A170P in the SHOX gene defines impaired nuclear translocation as a molecular cause for Léri–Weill dyschondrosteosis and Langer dysplasia

1-3 and encodes a paired related homeodomain transcription factor. Nominal levels of the SHOX protein have been implicated in bone development and longitudinal body growth, as heterozygous and homozygous loss of SHOX functions result in Leri-Weill dyschondrosteosis (LWD) and Langer dysplasia (LD), respectively. 45 Apart from mesomelic short stature and a characteristic deformity of the forearm leading to a limited mobility of the wrist (Madelung deformity), some individuals with LWD and LD present with a subset of clinical stigmata frequently observed in females with Turner syndrome, including high arched palate, curvature of radius/ulna/tibia, and short fourth metacarpals. 6-8 These clinical features are variable, leading to a significant phenotypic heterogeneity particularly among persons with LWD. 9 In addition, SHOX mutations are a major cause of isolated short stature conditions, with an estimated incidence of 2-3% in children presenting with idiopathic growth retardation. 10 11 This is higher than the incidence of achondroplasia and growth hormone deficiency together. 12 13