Chunyun Fu1, Shiyu Luo2, Xigui Long3, Yingfeng Li4, Shangyang She4, Xuehua Hu4, Meizhen Mo5, Zhanghong Wang5, Yuhua Chen5, Chun He5, Jiasun Su6, Yue Zhang6, Fei Lin6, Bobo Xie6, Qifei Li7, Shaoke Chen8. 1. 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. 2. 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. 3. National Laboratory of medical Genetics, Central South University, Changsha, 410000, China. 4. Medical Science Laboratory, Children's Hospital, 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. 5. Department of Pathology, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, China. 6. Department of Genetic Metabolism, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, China. 7. Department of Genetic Metabolism, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, China; Guangxi Huayin Medical Laboratory Center, Nanning 530012, China. Electronic address: sun2152002@gmail.com. 8. Department of Genetic Metabolism, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, China; Guangxi Huayin Medical Laboratory Center, Nanning 530012, China. Electronic address: chenshaoke123@163.com.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
OBJECTIVES: Defects in the humanGLI-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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Authors: Hugo Hernán Abarca Barriga; Felix Chavesta Velásquez; Claudia Barletta Carrillo; Abel Paucarmayta Tacuri; Margaret Bazán Hurtado; Tania Vásquez Loarte; Luis Ordoñez Rondón; Marco Ordoñez Linares; Evelina Andrea Rondón Abuhadba Journal: Rev Fac Cien Med Univ Nac Cordoba Date: 2022-06-06