Clement-Jones M, Schiller S, Rao E, Blaschke R J, Zuniga A, Zeller R, Robson S C, Binder G, Glass I, Strachan T, Lindsay S, Rappold G A
School of Biochemistry and Genetics, University of Newcastle upon Tyne, Ridley Building, Claremont Place, Newcastle NE1 7RU, UK.
Hum Mol Genet. 2000 Mar 22;9(5):695-702. doi: 10.1093/hmg/9.5.695.
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.
特纳综合征的特征是身材矮小，常伴有一系列不同的躯体特征，包括卵巢功能衰竭、心脏和肾脏异常、小颌畸形、肘外翻、高腭弓、掌骨短小和马德隆畸形。马德隆畸形也是莱尔-韦伊综合征的关键特征。此前已表明，假常染色体同源盒基因SHOX的缺陷会导致身材矮小和莱尔-韦伊综合征，并且SHOX单倍剂量不足被认为是导致特纳综合征身材矮小表型的原因。尽管进行了详尽的搜索，但未发现明显的SHOX直接小鼠同源基因。然而，SHOX与3号染色体上的SHOX2同源盒基因密切相关，后者有一个小鼠对应基因Og12x。我们分析了人类胚胎发育过程中SHOX和SHOX2的表达，并将其表达模式与Og12x的表达模式进行了对比。SHOX在四肢以及第一和第二咽弓中的表达模式不仅解释了与SHOX相关的身材矮小表型，而且首次为该基因参与其他特纳综合征体征的发育提供了证据。这一点在患有SHOX无义突变的患者中出现特纳综合征特征性骨骼畸形特征时得到了有力支持。
