Human Molecular Genetics, 2000, Vol. 9, No. 5 695-702
© 2000 Oxford University Press
The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome
School of Biochemistry and Genetics, University of Newcastle upon Tyne, Ridley Building, Claremont Place, Newcastle NE1 7RU, UK, 1Institute of Human Genetics, Ruprecht-Karls-University, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany, 2Department of Developmental Biology, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands, 3Department of Fetal Medicine, University of Newcastle upon Tyne, Newcastle, UK, 4Section of Paediatric Endocrinology at the Children’s Hospital, Tübingen University, Hoppe-Seyler-Straße 1, 72076 Tübingen, Germany and 5Clinical Genetics, Royal Children’s Hospital, Herston Road, Herston, Brisbane, Queensland 4029, Australia
Turner syndrome is characterized by short stature and is frequently associated with a variable spectrum of somatic features including ovarian failure, heart and renal abnormalities, micrognathia, cubitus valgus, high-arched palate, short metacarpals and Madelung deformity. Madelung deformity is also a key feature of Leri–Weill syndrome. Defects of the pseudoautosomal homeobox gene SHOX were previously shown to lead to short stature and Leri–Weill syndrome, and haploinsufficiency of SHOX was implicated to cause the short stature phenotype in Turner syndrome. Despite exhaustive searches, no direct murine orthologue of SHOX is evident. SHOX is, however, closely related to the SHOX2 homeobox gene on 3q, which has a murine counterpart, Og12x. We analysed SHOX and SHOX2 expression during human embryonic development, and referenced the expression patterns against those of Og12x. The SHOX expression pattern in the limb and first and second pharyngeal arches not only explains SHOX-related short stature phenotypes, but also for the first time provides evidence for the involvement of this gene in the development of additional Turner stigmata. This is strongly supported by the presence of Turner-characteristic dysmorphic skeletal features in patients with SHOX nonsense mutations.
+ To whom correspondence should be addressed. S.L. (human embryonic expression studies)—Tel: +44 191 222 6827; Fax: +44 191 222 6662; Email: s.lindsay@newcastle.ac.uk; G.A.R. (SHOX and Turner syndrome)—Tel: +49 6221 565059; Fax: +49 6221 565332; Email: gudrun_rappold@med.uni-heidelberg.de
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