Batjargal Khishigjargal, Tajima Toshihiro, Fujita-Jimbo Eriko, Yamaguchi Takeshi, Nakamura Akie, Yamagata Takanori
Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
Department of Pediatrics, School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia.
Clin Pediatr Endocrinol. 2022;31(4):234-241. doi: 10.1297/cpe.2021-0065. Epub 2022 Jul 7.
Paired box transcription factor 8 () is essential for thyroid organogenesis and development. Heterozygous pathogenic variants of typically cause congenital hypothyroidism (CH) due to thyroid hypoplasia. Additionally, pathogenic variants have been identified in patients with gland (GIS). This study was conducted to analyze the functional consequences of four variants (p.D94N, p.E90del, p.V58I, and p.L186Hfs22) previously identified in patients with CH and GIS. The transcriptional activity of variants on the thyroglobulin () promoter was assessed in a luciferase reporter assay. The levels of transcriptional activity on the promoter of p.E90del and p.L186Hfs22 were significantly reduced, whereas p.D94N and p.V58I showed residual activation. In addition, a dominant negative effect on the wild-type (WT) was not detected in any variant using a luciferase reporter assay. Two variants (p.E90del and p.L186Hfs*22) may be pathogenic causes of CH with GIS.
配对盒转录因子8（）对甲状腺器官发生和发育至关重要。的杂合致病变异通常由于甲状腺发育不全导致先天性甲状腺功能减退症（CH）。此外，在腺体异位症（GIS）患者中也发现了致病变异。本研究旨在分析先前在CH和GIS患者中鉴定出的四种变异（p.D94N、p.E90del、p.V58I和p.L186Hfs22）的功能后果。通过荧光素酶报告基因测定评估变异对甲状腺球蛋白（）启动子的转录活性。p.E90del和p.L186Hfs22对启动子的转录活性水平显著降低，而p.D94N和p.V58I表现出残余激活。此外，使用荧光素酶报告基因测定在任何变异中均未检测到对野生型（WT）的显性负效应。两种变异（p.E90del和p.L186Hfs*22）可能是CH合并GIS的致病原因。
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