Fan Xin, Fu Chunyun, Shen Yiping, Li Chuan, Luo Shiyu, Li Qifei, Luo Jingsi, Su Jiasun, Zhang Shujie, Hu Xuyun, Chen Rongyu, Gu Xuefan, Chen Shaoke
Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, People's Republic of China.
Endocrinology and Genetic Metabolism of Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092,China.
Clin Chim Acta. 2017 May;468:76-80. doi: 10.1016/j.cca.2017.02.009. Epub 2017 Feb 16.
Gene variants have been reported to be associated with congenital hypothyroidism (CH), the purpose of this study was to analyze the mutation spectrum and prevalence of 12 known causative genes (TSHR, PAX8, NKX2.1, NKX2.5, FOXE1, DUOX2, TG, TPO, GLIS3, NIS, SLC26A4 and DEHAL1) in CH in China.
Peripheral venous blood samples were collected from the patients. Genomic DNA was extracted from peripheral blood leukocytes. All exons and their exon-intron boundary sequences of the 12 known CH associated genes in 66 CH patients were screened by next-generation sequencing (NGS).
NGS analysis of 12 known CH associated genes revealed that 32 patients (32/66, 48.5%) were detected to have at least one potentially functional variant. 21, 9, 1, 1, 1 and 1 patients were found to have potential pathogenic variants in DUOX2, TG, PAX8, SLC26A4, TSHR and TPO genes, respectively. Novel variants included one DUOX2 and one TPO missense variants of unknown significance (VUS).
Our study expands the mutation spectrum of DUOX2 and TPO genes. 48.5% CH patients had at least one potential pathogenic variant. We found relatively high frequency of DUOX2 (31.8%) and TG (13.6%) mutations in our cohort.
已有报道称基因变异与先天性甲状腺功能减退症（CH）相关，本研究旨在分析中国CH患者中12个已知致病基因（TSHR、PAX8、NKX2.1、NKX2.5、FOXE1、DUOX2、TG、TPO、GLIS3、NIS、SLC26A4和DEHAL1）的突变谱及患病率。
采集患者外周静脉血样本。从外周血白细胞中提取基因组DNA。通过二代测序（NGS）对66例CH患者中12个已知CH相关基因的所有外显子及其外显子-内含子边界序列进行筛查。
对12个已知CH相关基因的NGS分析显示，32例患者（32/66，48.5%）被检测到至少有一个潜在的功能性变异。分别有21、9、1、1、1和1例患者在DUOX2、TG、PAX8、SLC26A4、TSHR和TPO基因中发现潜在的致病变异。新的变异包括一个意义未明的DUOX2错义变异和一个TPO错义变异（VUS）。
我们的研究扩展了DUOX2和TPO基因的突变谱。48.5%的CH患者至少有一个潜在的致病变异。我们发现在我们的队列中DUOX2（31.8%）和TG（13.6%）突变的频率相对较高。
