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目的先天性甲状腺功能减退(CH)是小儿最常见内分泌疾病之一。在已经发现的多种由于甲状腺激素合成与分泌的酶基因突变而导致CH中,以常染色体隐性方式遗传的DUOX2基因突变越来越受到国外学者关注,然而目前国内却没有该方面研究。研究中国人群CH患者常见的DUOX2基因突变类型和特点,不仅有利于CH患者的早期诊断或症状前诊断,而且有利于开展产前诊断,提高出生人口素质。方法本研究利用来自8例甲状腺肿大CH患者为研究对象,对DUOX2基因的全部外显子进行基因突变筛查,结合测序验证及生物信息学分析,研究中国人群CH患者常见的DUOX2基因突变类型和特点。结果 8例甲状腺肿大CH患者均没有发现DUOX2基因致病突变。但是在这些样本中,检测到3个氨基酸的改变,经过生物信息学分析后发现这些氨基酸的改变均位于DUOX2基因的非保守性位点,为新的多态性的改变,而不是引起CH的致病突变。在样本2中,DUOX2基因第三外显子中脯氨酸被亮氨酸取代,即DUOX2 c227 C>T(P76L),样本5中DUOX2基因第十三外显子发生同义突变,即DUOX2 c1621 C>A(R541R),样本6中,DUOX2基因第二十六外显子中赖氨酸被精氨酸取代,即DUOX2 c3532 A>G(K1178R)。结论 DUOX2基因在中国先天性甲状腺功能减退症伴甲状腺肿大的患儿中突变率极低,并不是引起伴甲状腺肿大的CH的常见致病基因。
Purpose Congenital hypothyroidism (CH) is one of the most common endocrine disorders in children. DUOX2 gene mutations inherited in an autosomal recessive manner have been attracting more and more scholars’ attention in many CHs, which have been found to be caused by the mutation of enzyme genes involved in the synthesis and secretion of thyroid hormone. However, at present, there is no such study in China. Studying the types and features of common DUOX2 mutations in Chinese CH patients is not only beneficial to the early diagnosis or pre-symptomatic diagnosis of CH patients, but also conducive to prenatal diagnosis and improve the quality of birth population. Methods In this study, 8 CHD patients with goiter were enrolled in this study. All the exons of DUOX2 gene were screened by gene mutation. Combined with sequencing validation and bioinformatics analysis, the genotypes of DUOX2 mutations in Chinese CH patients were studied And features. Results No mutations in DUOX2 gene were found in 8 cases of CH patients with goiter. However, in these samples, three amino acid changes were detected. After bioinformatics analysis, these amino acid changes were found in the non-conserved sites of the DUOX2 gene, which were new polymorphic changes rather than CH Pathogenic mutation. In sample 2, the proline in the third exon of DUOX2 was replaced by leucine (DUOX2 c227 C> T (P76L)), and the synonymous mutation in the thirteenth exon of DUOX2 gene in sample 5 was DUOX2 In sample 6, lysine in the twenty-six exon of the DUOX2 gene was replaced with arginine, ie, DUOX2 c3532 A> G (K1178R). Conclusions The DUOX2 gene has a very low mutation rate in children with congenital hypothyroidism and thyroid enlargement in China. It is not a common virulence gene that causes CH with thyroid enlargement.