中文摘要：

目的 研究伴异位的甲状腺发育不全（TD）患儿中NKX2.5基因的突变情况和遗传特征,完善NKX2.5基因突变库,并为基因诊断与产前诊断奠定应用基础.方法 通过山东省新生儿筛查系统选取山东省90例已排除先天性疾病（特别是先天性心脏病）的伴异位TD病例,提取外周静脉血基因组DNA,采用3对序列特异性引物对NKX2.5基因的全部2个外显子进行PCR扩增,测序后进行突变筛查.运用独立的2组二分类资料比较方法对扩增区域内所发现SNP位点的基因频率进行x2检验.结果 在伴异位的TD病例中未发现NKX2.5基因外显子区及外显子与内含子接头区存在突变,但在第1外显子区发现1个SNP位点（rs2277923,c.63T＞C）为同义突变（Glu→Glu）,经统计,90例伴异位的TD病例中SNPrs2277923的等位基因频率为T=0.416 7,与MAF最小等位基因频率比较,差异无统计学意义（x2=3.437 6,P＞0.05）,提示该SNP位点与TD的发生无相关性.结论 该研究是迄今为止国内关于伴异位的TD病例的最大规模的致病基因的筛查,未见突变存在,证实伴异位的TD病例中NKX2.5基因突变率极低,不是山东地区CH病例的致病基因.

英文摘要：

Objective The study focused on NKX2.5 gene mutations of thyroid dysgenesis （TD） with ectopy,in order to enrich the NKX2.5 gene mutation library and provide some evidence for gene diagnosis and prenatal diagnosis.Methods Blood samples were collected from 90 TD patients with ectopy who had been proved to exclude other congenital diseases,especially congenital heart disease.Genomic DNA was extracted from peripheral blood leukocytes.The whole 2 exons of gene NKX2.5 were amplified with 3 pairs of primers using PCR and direct sequencing to find new mutation types of gene NKX2.5.A x2 test was used to find whether there was an association between the single nucleotide poymorphism（SNP） and the disease.Results Analysis of NKX2.5 in 90 TD patients with ectopy revealed no mutations in the area of both exons and joint area between exons and introns.Nevertheless,a SNP（rs2277923,c.63T 〉 C）which was demonstrated to be a synonymous mutation（Glu→Glu） was found in exon 1,and the allele frequency of this SNP was T =0.416 7.It was demonstrated to have no significant difference with the allele frequency of minor allele frequency（MAF） minor allele count（x2 =3.437 6,P 〉 0.05）,suggesting that there might not be any correlation between this rs2277923 and TD.Conclusions It has never been reported to screen the volunteer genes for congenital hypothyroidism（CH） in such a mass of patients with ectopy in China,and the quantity is also at the forefront in the world.The data suggest that NKX2.5 mutations are highly rare in TD patients with ectopy and do not serve as the main cause of congenital hypothyroidism in Shandong province.