Abstract: Objective To screen nicotinamide nucleotide transhydrogenase (NNT) mutation of Chinese Han children with congenital hypothyroidism (CH) from Shandong province,and to analyze the association between NNT and CH in order to provide theoretical basis for the diagnosis of CH. Methods Totally 50 Chinese Han children with CH from Shandong province were enrolled to complete NNT encoding regions screening.DNA was extracted from the blood,the NNT encoding regions amplified by PCR were sent for Sanger sequencing and theResults of Sanger sequencing were compared with the original sequence(NM_012343.3)in NCBI to identify mutations.Biological information analysis of the identified mutations had been down. Results NNTc.1475C＞T(p.A492V)was found in two patients and NNTc.2704C＞A(p.P902T)was carried in one patient.The former mutation might be not a pathogenic mutation while the later one might be pathogenic mutation according to the Polyphen value. Conclusion Maybe NNT mutation is not the main virulence gene of CH in Chinese Han patients from Shandong province and still needs further study with more patients.

Key words: congenital hypothyroidism, nicotinamide nucleotide transhydrogenase, mutation

摘要： 目的 探讨山东地区汉族儿童先天性甲状腺功能减低症(CH)烟酰胺核苷酸转氢酶(NNT)基因突变情况及其与CH的关系,为CH的诊断提供理论依据。方法 对50例来自山东地区的汉族CH患儿进行NNT基因编码区筛查。提取血液基因组DNA,PCR扩增NNT基因全部编码区后进行Sanger测序,将测序结果与NCBI中NNT基因编码区原序列(NM_012343.3)进行比对,检测这些患儿是否携带NNT基因突变并对发现的突变进行生物信息学分析。结果 2例患儿中发现了NNT基因c.1475C＞T(p.A492V)突变,1例患儿中发现NNT基因c.2704C＞A(p.P902T)突变,Polyphen值显示前者几乎无蛋白危害性,可能不是致病突变,而后者蛋白危害性较大,应为致病突变。结论 NNT基因突变可能不是山东汉族人群CH的主要病因,仍需扩大样本量进行研究。

关键词: 先天性甲状腺功能减低症, NNT基因, 基因突变