Yang Rulai, Lu Yijun, Yang Chenxi, Wu Xiaoyu, Feng Junqi, Zhu Ling, Shu Qiang, Jiang Pingping
The Children's Hospitals, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Institute of Genetics and Department of Human Genetics, Zhejiang University School of Medicine, Hangzhou, China.
Front Genet. 2021 Aug 12;12:694683. doi: 10.3389/fgene.2021.694683. eCollection 2021.
Congenital hypothyroidism (CH) is the most common neonatal metabolic disorder. Although it has been understood to be a monogenic disease, some CH patients are reported to carry two or more variants at different genes. Here, ten permanent congenital hypothyroidism (PCH) patients were retrospectively reviewed, with elevated levels of serum thyroid-stimulating hormone and levothyroxine dependence during follow-up between 2015 and 2019. Each affected individual carried digenic variants, which were heterozygous at two of pathogenic genes. In total, five pathogenic genes, and , were simultaneously identified in subjects that were involved in the same metabolic pathway: thyroid hormone biosynthesis. There were digenic variants at TSHR and DUOX2 combined in three patients, and combined in two patients, and combined in two patients, and combined in two patients, and and combined in one patient. Additionally, seven novel variants, c.679G>A, c.127A>T, c.608-619del, c.959T>C, c.2307G>A, and c.6759_6765del, and c.93T>G, were identified in these PCH patients. Along with a literature review on digenic variants in patients with CH, our findings illustrated the complexity of genetic etiology in CH.
先天性甲状腺功能减退症（CH）是最常见的新生儿代谢紊乱疾病。尽管它被认为是一种单基因疾病，但据报道，一些CH患者在不同基因上携带两个或更多变异。在此，对10例永久性先天性甲状腺功能减退症（PCH）患者进行了回顾性研究，这些患者在2015年至2019年的随访期间血清促甲状腺激素水平升高且依赖左甲状腺素。每例受累个体均携带双基因变异，在两个致病基因上为杂合子。总共在参与同一代谢途径（甲状腺激素生物合成）的受试者中同时鉴定出五个致病基因，即 和 。三名患者中TSHR和DUOX2存在双基因变异，两名患者中 和 存在双基因变异，两名患者中 和 存在双基因变异，两名患者中 和 存在双基因变异，一名患者中 和 存在双基因变异。此外，在这些PCH患者中鉴定出七个新变异，即 c.679G>A、 c.127A>T、c.608 - 619del、c.959T>C、 c.2307G>A、c.6759_6765del以及 c.93T>G。结合对CH患者双基因变异的文献综述，我们的研究结果说明了CH遗传病因的复杂性。
