Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, China.
J Endocrinol Invest. 2012 Nov;35(10):889-92. doi: 10.3275/8239. Epub 2012 Jan 31.
Congenital hypothyroidism (CH) is a neonatal endocrine disease with an incidence of 1:2000 to 1:4000 worldwide. In about 85% of patients CH is secondary to thyroid dysgenesis, but its pathogenesis remains unclear. Thyroid transcription factors, such as paired box transcription factor 8 (PAX8), play an important role in thyroid organogenesis and development.
To screen PAX8 mutations in Chinese CH patients and characterize the features of PAX8 mutations in China.
Blood samples were collected from 300 CH patients in Shandong Province, China, and genomic DNA was extracted from peripheral blood leukocytes. Using PCR and direct sequencing, exon 3 and exon 4 of PAX8 were analyzed.
Analysis of PAX8 in 300 CH patients revealed heterozygous missense mutations or variations in two unrelated patients; one was a known missense mutation G92A, resulting in an arginine to histidine substitution at codon 31, the other was a missense variation G122T, resulting in the substitution of a glycine at position 41 by a valine residue. The patient with the R31H mutation had CH with thyroid hypoplasia, while the patient with the G41V variation had CH with a eutopic and normal-sized thyroid gland.
We report a heterozygous missense mutation and a variation in PAX8 in two out of 300 unrelated Chinese CH patients, showing that the PAX8 mutation rate is very low in CH patients in China.
先天性甲状腺功能减退症（CH）是一种全球性新生儿内分泌疾病，发病率为 1:2000 至 1:4000。在大约 85%的患者中，CH 继发于甲状腺发育不全，但发病机制尚不清楚。甲状腺转录因子，如配对盒转录因子 8（PAX8），在甲状腺器官发生和发育中发挥重要作用。
在中国 CH 患者中筛选 PAX8 突变，并描述中国 PAX8 突变的特征。
收集来自中国山东省 300 例 CH 患者的血液样本，从外周血白细胞中提取基因组 DNA。采用 PCR 和直接测序法分析 PAX8 的外显子 3 和外显子 4。
对 300 例 CH 患者的 PAX8 分析显示，在 2 位无血缘关系的患者中存在杂合错义突变或变异；一位是已知的错义突变 G92A，导致密码子 31 处的精氨酸突变为组氨酸，另一位是错义变异 G122T，导致第 41 位甘氨酸残基被缬氨酸取代。携带 R31H 突变的患者患有甲状腺发育不全的 CH，而携带 G41V 变异的患者患有甲状腺位置正常、大小正常的 CH。
我们报告了 2 例 300 例无关中国 CH 患者中 PAX8 的杂合错义突变和变异，表明中国 CH 患者的 PAX8 突变率非常低。
