Sonichedgehog信号分子(SHH)是纤毛介导的信号通路中的关键分子,也是胚胎发育中的关键形态发生原。SHH的功能丧失变体与全前脑畸形之间的关联已得到充分确立。在老鼠实验中,SHH信号的减少或增加已被证明与面部中线的狭窄或过度扩张有关。分别。在这里,我们报告了两名SHH从头截短变异的无关患者,其表现为超端粒而非低端粒.第一个病人是一个13岁的女孩。她的面部特征包括过度近视,斜视,telechanthus,错牙合,额前带,和广泛的寡妇的高峰。她有临界发育迟缓和call体发育不全。她有SHH的废话变体:Chr7(GRCh38):g.155802987C>T,NM_000193.4:c.1302G>A,p.(Trp434*)。第二个病人是一个25岁的女孩。她的面部特征包括远大和宽寡妇的高峰。她有发育迟缓和call体发育不全。她有SHH的移码变体:Chr7(GRCh38):g.155803072_155803074delCGGinsT,NM_000193.4:c.1215_1217delCCGinsa,p.(Asp405Glufs*92)。超端化表型与与SHH功能丧失相关的原型性低电位-全前脑表型形成鲜明对比。我们得出的结论是,SHH的截断变体的子集可能与过度过度而不是过度过度相关。
Sonic hedgehog signaling molecule (SHH) is a key molecule in the cilia-mediated signaling pathway and a critical morphogen in embryogenesis. The association between loss-of-function variants of SHH and holoprosencephaly is well established. In mice experiments, reduced or increased signaling of SHH have been shown to be associated with narrowing or excessive expansion of the facial midline, respectively. Herein, we report two unrelated patients with de novo truncating variants of SHH presenting with
hypertelorism rather than hypotelorism. The first patient was a 13-year-old girl. Her facial features included
hypertelorism, strabismus, telecanthus, malocclusion, frontal bossing, and wide widow\'s peak. She had borderline developmental delay and agenesis of the corpus callosum. She had a nonsense variant of SHH: Chr7(GRCh38):g.155802987C > T, NM_000193.4:c.1302G > A, p.(Trp434*). The second patient was a 25-year-old girl. Her facial features included
hypertelorism and wide widow\'s peak. She had developmental delay and agenesis of the corpus callosum. She had a frameshift variant of SHH: Chr7(GRCh38):g.155803072_155803074delCGGinsT, NM_000193.4:c.1215_1217delCCGinsA, p.(Asp405Glufs*92). The
hypertelorism phenotype contrasts sharply with the prototypical hypotelorism-holoprosencephaly phenotype associated with loss-of-function of SHH. We concluded that a subset of truncating variants of SHH could be associated with
hypertelorism rather than hypotelorism.