先天性甲状腺功能减低症伴甲状腺肿大患儿甲状腺球蛋白基因突变研究

Investigation of the relationship between mutation of thyroglobulin gene and congenital hypothyroidism with goiter

目的研究先天性甲状腺功能减低症(简称先天性甲低,CH)伴甲状腺肿大患儿甲状腺球蛋白(thyroglobulin,TG)基因突变类型及特点,为基因诊断提供理论依据。方法对2012年1月至8月青岛市妇女儿童医院11例经新生儿筛查确诊为先天性甲低伴甲状腺肿患儿,采用PCR扩增并直接测序的方法,对TG基因的外显子7、14、22、33、38进行基因突变检测,结合测序验证及生物信息学分析,研究TG基因突变类型及特点。结果在11例先天性甲低伴甲状腺肿患儿中,没有发现TG基因突变,分别在1例患儿和6例患儿中发现TGc.3218-81T>G(rs853324,纯合)和c.3218-81T>G(rs853324,杂合)两个单核苷酸多态性位点。结论青岛地区先天性甲低伴甲状腺肿大患儿中,TG基因突变率极低,可能不是该地区先天性甲低伴甲状腺肿大的突变热点基因。

Objective To identify thyroglobulin （TG） gene mutation in patients with congenital hypothyroidism with goiter, in order to provide full evidence for gene diagnosis of congenital hypothyroidism. Methods Totally 11 patients with congenital hypothyroidism with goiter in Qingdao Women and Children hospital from Jan. 2012 to Aug. 2012 were enrolled in this study. The 7,14,22,33 and 38 exons of TG gene were amplified through PCR and the products were se- quenced directly. The type and characteristic of TG gene mutation in patients with congenital hypothyroidism with goiter in this region were analyzed. Results Two single nucleotide polymorphism of TG gene were identified, but no gene mu- tation was observed. TG c.3218-8lT 〉 G （rs 853324, homozygous）in 1 patient and c.3218-81T 〉 G （rs 853324, hetero- zygosis） in 6 patients were found. Conclusion The incidence of TG gene mutation is very low in patients with congeni- tal hypothyroidism with goiter from Qingdao City. It suggests that TG gene mutation may not serve as the mutation hotspot gene of congenital hypothyroidism with goiter in Qingdao City.