Human transcription factor SLUG: mutation analysis in patients with neural tube defects and identification of a missense mutation (D119E) in the Slug subfamily-defining region

Karolin Stegmann , Julia Boecker , Christian Kosan , August Ermert , Jürgen Kunz , Manuela C Koch
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引用次数: 27

Abstract

Studies in mouse, chicken and Xenopus have shown that Slug is selectively expressed in the dorsal part of the developing neural tube. Ablation and antisense experiments in chicken suggest that Slug may be an important factor during neural tube closure. We therefore investigated the role of Slug as a possible candidate contributing to the aetiology of neural tube defects (NTD) in humans. We characterised the genomic structure of human SLUG including determination of the exon–intron boundaries. The coding sequence of SLUG was screened for mutations in 150 patients with NTD using single strand conformation analysis (SSCA). In one patient, we identified a missense mutation 1548C→A in exon 2 causing an exchange of a conserved amino acid (D119E) in the Slug subfamily-defining region preceding the first zinc finger. This is the first description of a human mutation in the SLUG gene. In accordance with the findings in model organisms, the SLUG mutation may be causally related to the development of NTD in our patient and could be considered as a predisposing factor.

人转录因子SLUG:在神经管缺陷患者中的突变分析和SLUG亚家族定义区错义突变(D119E)的鉴定
对小鼠、鸡和非洲爪蟾的研究表明,Slug在发育中的神经管的背侧有选择性地表达。鸡的消融术和反义实验表明,Slug可能是神经管关闭的重要因素。因此,我们研究了Slug作为人类神经管缺陷(NTD)病因学可能的候选因素的作用。我们描述了人类SLUG的基因组结构,包括外显子-内含子边界的测定。利用单链构象分析(SSCA)对150例NTD患者的SLUG编码序列进行了突变筛选。在一个患者中,我们在第2外显子中发现了一个错义突变1548C→a,导致Slug亚家族定义区在第一个锌指之前交换了一个保守氨基酸(D119E)。这是对人类SLUG基因突变的首次描述。根据在模式生物中的发现,SLUG突变可能与我们患者NTD的发展有因果关系,可能被认为是一个易感因素。
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