先天性甲状腺功能减低症一家系DUOX2基因突变检测

Mutation detection of dual oxidase 2 gene in a Chinese family with congenital hypothyroidism

目的对一个先天性甲状腺功能减低症家系进行二元氧化酶2(DUOX2)基因突变研究。方法对该家系中4名成员采样并提取DNA,用wafergen验证检测先证者甲状腺过氧化物酶(TPO)基因、二元氧化酶2(DUOX2)基因和二元氧化酶成熟因子2(DUOXA2)基因。PCR扩增先证者DUOX2基因各外显子、外显子-内含子交界区以及3'端和5'端非翻译区,以DNA测序技术检测DUOX2基因突变,并与该家系中其他成员进行对照分析。结果先证者为DUOX2基因c.3200C>T突变和新的c.1708C>T突变的复合杂合子,其父亲为c.1708C>T突变杂合子,其母亲及胞姐均为c.3200C>T突变杂合子。结论 DUOX2基因突变是中国人群先天性甲状腺功能减低症发生的原因之一。

Objective： To identify dual oxidase 2 （DUOX2） gene mutations in a patient of a Chinese family with congenital hypothyroidism. Methods： Genomic DNA was isolated from peripheral blood samples of 1 patient and 3 healthy members in the pedigree.thyroid peroxidase （TPO） gene, dual oxidase 2 （DUOX2） gene and dual oxidase maturation factor 2 （DUOXA2） gene mutations were detected by wafergen technique. All of the exons and flanking introns of DUOX2 gene were amplified by PCR, then the PCR products were sequenced bi-directionally.Results： A missense mutation c.3200C〉T and a nonsense mutation c. 1708C〉T was found in DUOX2 gene of the patient. The father was heterozygous for the mutation c. 1708C〉T.The mother and elder sister were heterozygous for the mutation c.3200C〉T. Conclusions： DUOX2 gene mutation was one of the reasons which resulted in Chinese patients with congenital hypothyroidism.