先天性甲状腺功能减退症伴发育不全患儿TTF2（FOXE1）基因突变筛查研究

发布时间：2018-06-25 04:32

本文选题：先天性甲状腺功能减退症 + TTF2　；参考：《青岛大学》2016年硕士论文

【摘要】：目的筛查山东地区先天性甲状腺功能减退症(CH)伴甲状腺发育不全患儿转录因子2(TTF2)基因突变的类型及特点,为CH的基因诊断及早期治疗提供理论依据。方法选取2007年至2015山东地区90例CH伴甲状腺发育不全的患儿作为研究对象,分别来自90个无血缘关系的家庭,其中男29例,女61例,年龄(3.5±0.5)岁。入选标准:出生后2-3天的新生儿取足跟血首先检测促甲状腺激素(TSH)浓度作为初筛,若结果≥20μIU/m L,再检测静脉血测促甲状腺激素(TSH)、游离甲状腺素(FT4)游离三碘甲状腺原氨酸(FT3);超声检查显示甲状腺发育不全(包括缺如,异位,发育不良),确诊为CH;已排除患有其他先天性疾病。提取其外周静脉血基因组DNA,采用PCR扩增与直接测序的方法,对TTF2基因外显子进行突变筛查。结果90例CH伴甲状腺发育不全患者中,发现1个新的杂合子错义变体(c.A3401G,p.K1134R),携带该突变的患者表现为永久性甲减。同时发现了1个已知的single nucleotide polymorphisms SNP位点(rs755282859,C.483GA),该患者表现型为轻度的暂时性甲减。结论在对90例CH伴甲状腺发育不全患儿进行TTF2突变筛查中,共发现了1例新的TTF2变体和1例已知的SNP((rs755282859,C.483GA)。这是首次描述这个变体;TTF2基因在山东地区先天性甲状腺功能减退伴发育不全患者中突变率较低。
[Abstract]:Objective to screen the type and characteristics of TTF2 gene mutation in children with congenital hypothyroidism (Ch) and hypothyroidism in Shandong province, and to provide theoretical basis for the gene diagnosis and early treatment of Ch. Methods from 2007 to 2015, 90 children with Ch associated with hypothyroidism were selected from 90 unrelated families, including 29 males and 61 females aged (3.5 卤0.5) years. Inclusion criteria: the calcaneal blood samples were taken from the newborns 2-3 days after birth and the thyroid stimulating hormone (TSH) concentration was first detected as a primary screening. If the results were more than 20 渭 IU-mL, thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and hypothyroidism (including absence, ectopic) were detected in venous blood. Dysplasia), diagnosed as CH; other congenital diseases have been excluded. The genomic DNA of TTF2 gene was extracted from the peripheral venous blood. The mutation of TTF2 gene exon was screened by PCR amplification and direct sequencing. Results A new heterozygous missense variant (c. A3401G / K1134R) was found in 90 patients with Ch complicated with hypothyroidism. The patient with the mutation presented permanent hypothyroidism. At the same time, a known single nucleotide polymorphisms SNP locus (rs755282859, C.483GA) was found in this patient. The phenotype of the patient was mild transient hypothyroidism. Conclusion A new variant of TTF2 and a known SNP (rs7552859, C.483GA) were found in 90 cases of Ch with hypothyroidism. This is the first time to describe the low mutation rate of TTF2 gene in patients with congenital hypothyroidism and dysplasia in Shandong.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R725.8

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