Zou Hui, Chai Jian, Liu Shiguo, Zang Hongwei, Yu Xiaoxia, Tian Liping, Li Huichao, Han Bingjuan
Jinan Maternity and Child Health Care Hospital of Shandong University, Jinan 250100 Shandong, China ; Neonatal Disease Screening Center, Jinan Maternity and Child Health Care Hospital Jinan 250001, Shandong, China.
Department of Biochemistry and Molecular Biology, Qingdao University Qingdao 266021, Shandong, China.
Int J Clin Exp Pathol. 2015 Sep 1;8(9):11434-9. eCollection 2015.
Thyroid dysgenesis (TD) is the most frequent cause of congenital hypothyroidism (CH), but its pathogenesis remains unclear. As a thyroid transcription factor, paired box transcription factor 8 (PAX8) is essential for thyroid organogenesis and development.
To screen PAX8 mutations and characterize the features of these mutations in Chinese TD patients.
Blood samples were collected from 63 TD patients in Shandong Province, China, and genomic DNA was extracted from peripheral blood leukocytes. Exon 3~4 of PAX8 were analyzed by PCR and direct sequencing.
Direct sequencing of PAX8 revealed a heterozygous missense mutation (c.155G/C, P.Arg52Pro) in one child with agenesis. Genetic screening of the child's family revealed that the clinically unaffected parents do not carry the mutation, suggesting that the identified sequence change is a de novo mutation.
We report a heterozygous missense de novo mutation in PAX8 in one out of 63 unrelated Chinese TD patients, showing that the PAX8 mutation rate is very low in TD patients in China. However, de novo mutation and epigenetic mechanisms need to be considered in the future study.
甲状腺发育不全（TD）是先天性甲状腺功能减退症（CH）最常见的病因，但其发病机制仍不清楚。作为一种甲状腺转录因子，配对盒转录因子8（PAX8）对甲状腺器官发生和发育至关重要。
筛选中国TD患者中PAX8突变并描述这些突变的特征。
从中国山东省的63例TD患者中采集血样，从外周血白细胞中提取基因组DNA。采用聚合酶链反应（PCR）和直接测序法分析PAX8的第3至4外显子。
PAX8直接测序显示1例甲状腺缺如患儿存在杂合错义突变（c.155G/C，P.Arg52Pro）。对该患儿家庭的基因筛查显示，临床未受影响的父母不携带该突变，提示所鉴定的序列变化为新发突变。
我们报告了63例无亲缘关系的中国TD患者中有1例存在PAX8杂合错义新发突变，表明中国TD患者中PAX8突变率很低，但在未来研究中仍需考虑新发突变和表观遗传机制。
