C端结合蛋白(CtBP1/2)是在脊椎动物神经发育过程中发挥重要作用的转录共调节因子。本系统综述旨在确定与脑发育综合征相关的CTBP1和CTBP2遗传变异的病例报告。我们筛选了不同的数据库(PubMed,Scopus,谷歌学者,LILACS)通过系统地搜索期刊并检查参考列表和背景文件的引用。我们从五篇论文中发现了14例(10例男性),携带两种病原体,CTBP1基因中的杂合变体(13个个体携带错义突变c.991CT,p.Arg342Trp,和一个携带2个碱基对缺失c.1315_1316delCA的受试者,p.Gln439ValfsTer84)。这些突变在13例和1例母体生发镶嵌性中从头突变。两种变体在蛋白质的相同结构域中:Pro-Leu-Asp-Leu-Ser(PLDLS)C末端。这些突变的患者表现出智力障碍的表型,HADDTS综合征(低张力,共济失调,发育迟缓,和牙釉质缺陷),和小脑体积损失。我们没有发现与CTBP1中存在的纯合突变相关的报道病例。我们没有发现任何与杂合或纯合CTBP2突变相关的神经发育表型的报道。由于CTBP2/RIBEYE是一个具有双重功能的基因,识别和解释潜在的致病变异是具有挑战性的.Further,CTBP2基因中的纯合突变可能是致死的。由于这些蛋白质的变体而导致的神经发育的发病机制尚未阐明,尽管有一些功能性证据。应该进行进一步的研究以了解这些转录因子及其与彼此及其伴侣的相互作用。
C-terminal binding proteins (CtBP1/2) are transcriptional coregulators that play a significant role during vertebrate neurodevelopment. This systematic
review aims to identify case reports with genetic variants in CTBP1 and CTBP2 associated with brain development syndromes.We screened different databases (PubMed, Scopus, Google Scholar, LILACS) by systematically searching journals and checking reference lists and citations of background papers. We found fourteen cases (10 males) from five papers carrying two pathogenic, heterozygous variants in the CTBP1 gene (13 individuals carried the missense mutation c.991C T, p.Arg342Trp, and one subject carrying the 2-base pair deletion c.1315_1316delCA, p.Gln439ValfsTer84). These mutations were de novo in 13 cases and one case of maternal germinal mosaicism. Two variants are in the same domain of the protein: Pro-Leu-Asp-Leu-Ser (PLDLS) C terminal. Patients with these mutations exhibit a phenotype with intellectual disability, HADDTS syndrome (hypotonia, ataxia, developmental delay, and tooth enamel defects), and cerebellar volume loss. We did not identify reported cases associated with homozygous mutations harbored in CTBP1. We did not identify any report of neurodevelopment phenotypes associated with heterozygous or homozygous CTBP2 mutations. Due to CTBP2/RIBEYE being a gene with dual function, identifying and interpreting the potential pathogenic variants is challenging.Further, homozygous mutations in the CTBP2 gene may be lethal. The mechanisms involved in the pathogenesis of neurodevelopment due to variants of these proteins have not yet been elucidated, despite some functional evidence. Further studies should be conducted to understand these transcription factors and their interaction with each other and their partners.