先天性甲状腺功能减退伴甲状腺肿大患儿甲状腺球蛋白基因突变研究

发布时间：2018-03-18 16:18

本文选题：先天性甲状腺功能减退症　切入点：甲状腺肿大　出处：《青岛大学》2012年硕士论文　论文类型：学位论文

【摘要】：目的研究青岛地区先天性甲状腺功能减退(CH)伴甲状腺肿大患儿中甲状腺球蛋白(TG)基因的突变类型及特点,为基因诊断及早期治疗提供理论依据。方法研究对象共10例,均为在青岛市新生儿筛查中心,经筛查确诊为先天性甲状腺功能减退伴甲状腺肿大的患儿,平均年龄8.7±2.3岁,男3例,女7例,99mTc甲状腺扫描或甲状腺B超检查示甲状腺位置正常且甲状腺肿大患儿,且无甲状腺疾病家族史者。取其外周血并提取基因组DNA,采用聚合酶链反应(PCR)扩增TG基因全部外显子以及外显子与内含子结合区,利用DHPLC(变性高效液相色谱技术)高通量多态/突变筛选平台,对TG基因的PCR产物进行基因突变筛查,并对DHPLC分析后显示异常峰型的TG-PCR片段进行直接测序,验证突变位点或单核苷酸多态性位点,并通过生物信息学对突变位点进行分析,研究TG基因突变导致先天性甲减的可能机制。结果在试验组中进行TG基因突变筛查,共发现1种TG基因复合杂合突变(c.2687GA/c.7006CT,p.R877Q/p.R2317X)及2种单核苷酸多态性位点(c.2182TG,c.2334TC)。结论经过对10名先天性甲减伴甲状腺肿大患儿进行TG基因突变筛查,共发现1种TG基因复合杂合突变及2种单核苷酸多态位点,表明青岛地区先天性甲减伴甲状腺肿大患者中TG基因突变率较低。
[Abstract]:Objective to study the type and characteristics of TGG gene mutation in children with congenital hypothyroidism and goiter in Qingdao, and to provide theoretical basis for gene diagnosis and early treatment. All of them were diagnosed as congenital hypothyroidism with goiter in Qingdao Neonatal screening Center. The average age was 8.7 卤2.3 years old. Thyroid scan or B-mode ultrasonography showed normal thyroid position and goitre in 7 women. All exons of TG gene and the binding region between exon and intron were amplified by polymerase chain reaction (PCR). Using the high throughput polymorphic / mutation screening platform of denaturing high performance liquid chromatography (DHPLC), the PCR products of TG gene were screened for gene mutation, and the TG-PCR fragments with abnormal peak type were sequenced directly by DHPLC analysis. The mutation sites or single nucleotide polymorphisms were verified, and the mutation sites were analyzed by bioinformatics to study the possible mechanism of TG gene mutation leading to congenital hypothyroidism. A combined heterozygous mutation of TG gene was found in 10 children with congenital hypothyroidism associated with thyroid enlargement, and two single nucleotide polymorphisms (SNPs) were found in 10 children with congenital hypothyroidism associated with thyroid enlargement, and two single nucleotide polymorphic loci (SNP) were found in the total of c. 2687GA / c. 7006CTP p.R877Qp. R2317X. conclusion 10 children with congenital hypothyroidism and thyroid enlargement were screened for TG gene mutation. A combined heterozygous mutation of TG gene and two single nucleotide polymorphic loci were found, which indicated that the mutation rate of TG gene was lower in patients with congenital hypothyroidism and goiter in Qingdao area.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R725.8

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