Objective: To study the types and characteristics of TUBB1 mutation in children with congenital hypothyroidism (CH) and thyroid dysgenesis (TD) in Shandong, China.
Methods: Mutations of the whole coding region of the TUBB1 gene were analyzed for 289 children with CH and TD in Shandong. Whole-genome DNA was extracted from peripheral blood leukocytes. PCR multiplication was performed for the whole coding region of the TUBB1 gene. Sanger sequencing was performed for the PCR products, and a biological information analysis was performed.
Results: Among the 289 children with CH and TD, 4 (1.4%) were found to have a c.952C>T(p.R318W) heterozygous mutation in the TUBB1 gene, resulting in the change of tryptophan into arginine at codon 318 of TUBB1 protein. This mutation was evaluated as "potentially pathogenic" based on the classification criteria and guidelines for genetic variation by American College of Medical Genetics and Genomics.
Conclusions: A novel mutation is detected in the exon of the TUBB1 gene in children with CH and TD in Shandong, suggesting that the TUBB1 gene may be a candidate pathogenic gene for CH children with TD.
目的: 探讨山东地区先天性甲状腺功能减低症（CH）伴甲状腺发育不全（TD）患儿TUBB1基因突变的类型和特点。
方法: 对山东地区289例确诊CH伴TD患儿进行TUBB1基因全编码区突变研究。提取患儿外周血全基因组DNA，PCR扩增TUBB1基因全编码区，对扩增产物进行Sanger测序，并进行生物信息学分析。
结果: 289例CH伴TD患儿中发现4例（1.4%）TUBB1基因存在c.952C > T（p.R318W）杂合变异，导致TUBB1蛋白第318位色氨酸变成精氨酸，根据美国医学遗传学与基因组学学会遗传变异分类标准与指南，该变异评级为"可能致病的"。
结论: 在山东地区CH伴TD患儿中发现了新的TUBB1基因变异，提示TUBB1基因可能是CH伴TD的候选致病基因。