Objective: To investigate the characteristics of DUOXA2 gene mutation and the genotype-phenotype relationship in children with congenital hypothyroidism (CH) in Guangzhou, China.
Methods: A total of 20 CH patients with suspected thyroid dyshormonogenesis who had no DUOX2 gene mutation were enrolled. These patients who were born between 2011 and 2012 were screened and diagnosed with CH in the Guangzhou Newborn Screening Center. PCR and direct sequencing were used to analyze DUOXA2 gene mutation.
Results: Among the 20 patients, 2 had p.Y246X/p.Y246X homozygous mutation; 4 had monoallelic heterozygous mutation, among whom 2 carried the known pathogenic mutation c.413-414insA, 1 carried p.Y246X, and 1 carried a novel mutation, p.G79R. Reevaluation was performed at the age of 2-3 years, and the results showed that the two patients with p.Y246X/p.Y246X homozygous mutation were manifested as transient and mild permanent CH, respectively. Among the four patients with monoallelic heterozygous mutation, the one who carried p.Y246X mutation was manifested as typical permanent CH, and the other three were manifested as transient CH.
Conclusions: DUOXA2 gene mutation is a common molecular pathogenic basis for CH children with suspected thyroid dyshormonogenesis in Guangzhou, and most of them are manifested as transient CH. There is no association between DUOXA2 genotypes and phenotypes. The novel mutation p.G79R is probably a pathogenic mutation.
目的: 探讨广州地区先天性甲状腺功能减低症（CH）患儿DUOXA2基因突变特点及其基因型与表型的关系。
方法: 采用PCR及直接测序法，对2011年至2012年出生、广州市新生儿筛查中心诊断并排除DUOX2基因突变的20例疑似甲状腺激素合成障碍的CH患者进行DUOXA2基因突变分析。
结果: 20例CH患者中2例为p.Y246X/p.Y246X纯合突变；4例为单等位基因杂合突变：分别为已知致病突变c.413-414insA携带者2例，p.Y246X携带者1例，新突变p.G79R携带者1例。2~3岁再评估时显示，2例p.Y246X/p.Y246X纯合突变者分别表现为暂时性CH及轻度永久性CH；4例单等位基因突变者，除1例p.Y246X携带者表现为典型永久性CH外，其余3例携带者均为暂时性CH。
结论: DUOXA2基因突变是广州地区疑似甲状腺激素合成障碍性CH患儿较常见的分子发病基础，多数表现为暂时性CH，未发现DUOXA2基因型与表型的关系。新突变p.G79R为致病性突变的可能性大。