Tibial hemimelia associated with GLI3 truncation
Tibial hemimelia associated with GLI3 truncation
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DOI：
10.1038/jhg.2015.161
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发表时间：
2016-05-01
影响因子：
3.5
通讯作者：
Hopyan, Sevan
中科院分区：
文献类型：
--
作者：
Deimling, Steven;Sotiropoulos, Chris;Hopyan, Sevan
胫骨偏瘫是一种罕见的，使人衰弱的，通常是散发性的先天性缺陷。在综合征病例中，已经鉴定出Sonic hedgehog （SHH）增强子的突变。在这里，我们描述了在两例双侧胫骨偏瘫患者中SHH抑制因子GLI3中类似的5kb缺失。这种缺失导致GLI3蛋白被截断，缺乏dna结合结构域，不能抑制hedgehog信号传导。这些发现加强了胫骨偏瘫的概念，即由于未能将SHH活动限制在肢体芽的后部而产生。
Tibial hemimelia is a rare, debilitating and often sporadic congenital deficiency. In syndromic cases, mutations of a Sonic hedgehog (SHH) enhancer have been identified. Here we describe an similar to 5 kb deletion within the SHH repressor GLI3 in two patients with bilateral tibial hemimelia. This deletion results in a truncated GLI3 protein that lacks a DNA-binding domain and cannot repress hedgehog signaling. These findings strengthen the concept that tibial hemimelia arises because of failure to restrict SHH activity to the posterior aspect of the limb bud.