The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome
The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome
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DOI：
10.1093/hmg/9.5.695
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发表时间：
2000-03-22
影响因子：
3.5
通讯作者：
Rappold, GA
中科院分区：
文献类型：
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作者：
Clement-Jones, M;Schiller, S;Rappold, GA
Turner综合征以身材矮小为特征，通常与多种躯体特征相关，包括卵巢功能衰竭、心脏和肾脏异常、小颌畸形、肘外翻、高弓腭、掌骨短和马德隆畸形，马德隆畸形也是Leri-Weill综合征的一个关键特征，假常染色体同源盒基因SHOX的缺陷曾被证明会导致身材矮小和Leri-Weill综合征。并且SHOX的单倍性不足可能导致Turner综合征的身材矮小表型，尽管进行了详尽的搜索，但没有明显的SHOX的直接小鼠同源物。然而，SHOX与3q上的SHOX2同源盒基因密切相关，后者在小鼠中有一个对应的基因Og12x。我们分析了人类胚胎发育过程中SHOX和SHOX2的表达，并将其与Og12x的表达模式进行了比较。肢体和第一、第二咽弓的SHOX表达模式不仅解释了SHOX相关的矮小表型，而且首次为该基因参与额外特纳柱头的发育提供了证据。SHOX无义突变患者中存在特纳特征的畸形骨骼特征有力地支持了这一点。
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.