Microdeletion in the SHOX 3′ region associated with skeletal phenotypes of Langer mesomelic dysplasia in a 45,X/46,X,r(X) infant and Leri–Weill dyschondrosteosis in her 46,XX mother: Implication for the SHOX enhancer

It is known that SHOX nullizygosity results in Langer mesomelic dysplasia (LMD) and SHOX haploinsufficiency leads to Leri–Weill dyschondrosteosis (LWDC). Here, we report on a microdeletion in the SHOX 3′ region identified in a Japanese infant with LMD‐compatible skeletal features and a 45,X[191]/46,X,r(X)(p22.3q24)[9] karyotype and in her mother with LWDC‐compatible skeletal features and a normal 46,XX karyotype. Physical and auxological examinations revealed mesomelic appearance, ulnarly deviated hands, and borderline micrognathia in the infant, and relatively short forearms and lower legs in the mother. Radiological studies indicated mesomelia, markedly curved radii, hypoplastic ulnas and fibulas, and metaphyseal splaying in the infant, and borderline to mild curvature of the radii, decreased carpal angles, and high‐normal triangularization index in the mother. Cytogenetic and molecular studies showed that the ring X chromosome of the infant was missing SHOX and of paternal origin, whereas the cytogenetically normal X chromosomes of the infant and one of the two X chromosomes of the mother, though they retained SHOX with normal coding sequences, had a microdeletion in the SHOX 3′ region. The microdeletion started from a position ∼200 kb from SHOX coding sequences, and spanned 240–350 kb in physical length involving DXYS233. The results, in conjunction with those reported by Flanagan et al. [2002], suggest that a cis‐acting enhancer exists in the SHOX 3′ region around DXYS233. © 2005 Wiley‐Liss, Inc.