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[目的]探讨先天性甲状腺功能减退症(CH)患儿TSHR、PAX8、TTF1、TTF2 和 NKX2.5 的基因突变情况,分析基因突变的类型和特点,为其新生儿的早期筛查和临床基因诊断的开展提供参考.[方法]提取 14 例CH 患儿的基因组DNA,对TSHR、PAX8、TTF1、TTF2、NKX2.5 基因的全部外显子基因进行 PCR扩增;再利用二代测序方法对上述基因扩增产物进行测序.[结果]9 例 CH 患儿检测到了突变位点,其中在TSHR基因上发现了 5 种可疑致病的基因突变,在 PAX8 基因上发现了 2 种可疑致病的基因突变,在 TTF1基因和 TTF2 基因上分别发现了 1 种可疑致病基因突变,在 NKX2 .5 基因上未发现可疑致病基因突变.[结论]CH 患儿的已知候选基因TSHR、PAX8、TTF1 和TTF2 上均存在基因突变并且进一步扩大了 TSHR基因的突变谱,但其基因型与表现型的具体关系尚不能明确,仍需要大量的功能实验加以验证.“,”[Obj ective]To investigate the gene mutations of TSHR,PAX8,TTF1 ,TTF2 and NKX2 .5 in children with congenital hypothyroidism (CH),and to analyze the types and characteristics of gene mutations, so as to provide reference for early screening and clinical gene diagnosis of neonates.[Methods]Genomic DNA was extracted from 1 4 children with CH and all exons of TSHR,PAX8,TTF1 ,TTF2 and NKX2 .5 genes were amplified by PCR.The amplified products were sequenced by second generation sequencing.[Results]The mutation sites were detected in 9 children with CH.Five suspicious pathogenic gene mutations were found in TSHR gene,two suspicious pathogenic gene mutations were found in PAX8 gene,one suspicious pathogenic gene mutation was found in TTF1 gene and TTF2 gene respectively,and no suspicious pathogenic gene muta-tion was found in NKX2.5 gene.[Conclusions]The known candidate genes TSHR,PAX8,TTF1 and TTF2 in children with CH all have gene mutations and further enlarged the mutation spectrum of TSHR gene.Howev-er,the specific relationship between genotype and phenotype is still unclear,and a large number of functional experiments are needed to verify it.