Background:The transcription factor paired box 8 (PAX8) was associated with type 2 congenital non-goitrous hypothyroidism (CHNG2), a clinical phenotype of congenital hypothyroidism (CH). Though studied in a few regions with different ethnicities, the incidence of PAX8 mutations varied, even among Chinese cohorts in different regions. This study aimed to identify and characterize PAX8 mutations and explore the prevalence of its mutations in another cohort of CH. Methods: The 105 unrelated Chinese patients with CH were collected from four major hospitals. Exomes of the 105 samples were sequenced by Hiseq 2000 platform to identify mutations of PAX8 on genomic DNAs extracted from peripheral blood samples. Luciferase reporter assays were used to assess the effects of mutations on the transcription of thyroid peroxidase (TPO). Results: Three PAX8 mutations in four subjects were identified in 105 samples. One variant, rsl 89229644, was detected in two subjects, and categorized as uncertain significance. The other two missense mutations (275T>C/Ile92Thr and 398G>A/Argl33Gln) were not detected in three large-scale genotyping projects, namely 1000 Genome Project, Exome Aggregation Consortium and GO Exome Sequencing Project. Functional studies for the two mutations revealed that they could impair the transcription ability of PAX8 on one of its target genes, TPO. Therefore, the two mutations were causative for the pathogenesis of CHNG2. After combining the studies of PAX8 mutations, an average frequency of 1.74%(21/1209) could be obtained in Chinese patients with CH. Conclusion: The study specifically demonstrates the role of two mutations in impairing the transcription ability of PAX8, which should be considered as pathogenic variants for CH.
Fang QianGui-Yu LiXiang-Jun WuQin JiaGuan-Ting LyuMan-Li WangJun Wang
目的 观察转录因子ZBTB18对结直肠癌细胞的生长的影响。方法 从NCBI GEO数据库中下载肿瘤基因表达芯片数据,对ZBTB18基因的表达水平进行分析;同时通过RNA干扰和Transwell实验研究ZBTB18对结直肠癌细胞迁移的影响。结果 ZBTB18蛋白表达于结直肠癌细胞系,且高转移能力的细胞系中该蛋白的表达水平远高于原发性结直肠癌肿瘤细胞系( P <0.05)。RNA干扰试验可特异性地显著沉默结直肠癌细胞HT29中ZBTB18的表达,Transwell实验发现在ZBTB18沉默后HT29细胞的侵袭和迁移能力显著降低( P <0.05)。结论 转录因子ZBTB18可以促进结直肠癌细胞的侵袭与迁移,可能参与结直肠癌的转移。
