Medical Science Laboratory, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, China; Department of Pathology, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, China; Department of Genetic Metabolism, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, China; Birth Defects Prevention and Control Institute of Guangxi Zhuang Autonomous Region, Nanning 530003, China.
Department of Genetic Metabolism, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, China; Birth Defects Prevention and Control Institute of Guangxi Zhuang Autonomous Region, Nanning 530003, China.
Clin Chim Acta. 2018 Jan;476:38-43. doi: 10.1016/j.cca.2017.11.011. Epub 2017 Nov 13.
Defects in the human GLI-similar 3 (GLIS3) gene are reported to be a rare cause of congenital hypothyroidism (CH) and neonatal diabetes. The aim of this study was to examine the prevalence of GLIS3 mutation among CH patients in the Guangxi Zhuang Autonomous Region of China and to define the relationships between GLIS3 genotypes and clinical phenotypes.
Blood samples were collected from 592 patients with CH in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the GLIS3 gene with their exon-intron boundaries were screened by next-generation sequencing (NGS) and CNVplex®. Chromosomal microarray analysis (CMA) was performed to detect the existence of the adjacent gene deletion.
NGS and CNVplex® analysis of GLIS3 in 592 CH patients revealed two different variations in two individuals (2/592, 0.3%). Patient 1 was the paternal allele of 9p24.3p23 heterozygous deletion including the whole GLIS3 gene, and patient 2 was heterozygous for c.2159G>A (p.R720Q) GLIS3 variant combined with compound heterozygous DUOX2 mutations (p.R683L/p.L1343F).
Our study indicated that the prevalence of GLIS3 variations was 0.3% among studied Chinese CH patients. Multiple variations in one or more CH associated genes can be found in one patient. We found a novel GLIS3 variation c.2159G>A (p.R720Q), thereby expanding the variation spectrum of the gene.
人类 GLI 相似 3（GLIS3）基因的缺陷据报道是先天性甲状腺功能减退症（CH）和新生儿糖尿病的罕见原因。本研究旨在研究 GLIS3 突变在中国广西壮族自治区 CH 患者中的流行情况，并定义 GLIS3 基因型与临床表型之间的关系。
收集中国广西壮族自治区 592 例 CH 患者的血样，并从外周血白细胞中提取基因组 DNA。通过下一代测序（NGS）和 CNVplex®对 GLIS3 基因的所有外显子及其外显子-内含子边界进行筛选。进行染色体微阵列分析（CMA）以检测相邻基因缺失的存在。
对 592 例 CH 患者的 GLIS3 进行 NGS 和 CNVplex®分析，在 2 例患者（2/592，0.3%）中发现了两种不同的变异。患者 1 为 9p24.3p23 杂合缺失的父本等位基因，包括整个 GLIS3 基因，患者 2 为杂合 c.2159G>A（p.R720Q）GLIS3 变异与复合杂合 DUOX2 突变（p.R683L/p.L1343F）。
我们的研究表明，在所研究的中国 CH 患者中，GLIS3 变异的患病率为 0.3%。一个或多个 CH 相关基因中的多种变异可能存在于一个患者中。我们发现了一种新的 GLIS3 变异 c.2159G>A（p.R720Q），从而扩展了该基因的变异谱。
