title: Thyroglobulin gene mutations in Chinese patients with congenital hypothyroidism.
abstract: Mutations in Thyroglobulin (TG) are common genetic causes of congenital hypothyroidism (CH). But the TG mutation spectrum and its frequency in Chinese CH patients have not been investigated. Here we conducted a genetic screening of TG gene in a cohort of 382 Chinese CH patients. We identified 22 rare non-polymorphic variants including six truncating variants and 16 missense variants of unknown significance (VUS). Seven patients carried homozygous pathogenic variants, and three patients carried homozygous or compound heterozygous VUS. 48 out of 382 patients carried one of 18 heterozygous VUS which is significantly more often than their occurrences in control cohort (P < 0.0001). Unique to Asian population, the c.274+2T>G variant is the most common pathogenic variant with an allele frequency of 0.021. The prevalence of CH due to TG gene defect in Chinese population was estimated to be approximately 1/101,000. Our study uncovered ethnicity specific TG mutation spectrum and frequency.
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China; Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Xuyun
authors.initials: X
authors.lastname: Hu
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Rongyu
authors.initials: R
authors.lastname: Chen
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Chunyun
authors.initials: C
authors.lastname: Fu
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fan
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Jiale
authors.initials: J
authors.lastname: Qian
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Shang
authors.initials: S
authors.lastname: Yi
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Jingsi
authors.initials: J
authors.lastname: Luo
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Jiasun
authors.initials: J
authors.lastname: Su
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Bobo
authors.initials: B
authors.lastname: Xie
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
authors.forename: Hongdou
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Xuefan
authors.initials: X
authors.lastname: Gu
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China. Electronic address: chenshaoke123@163.com.
authors.forename: Shaoke
authors.initials: S
authors.lastname: Chen
authors.affiliation: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China; Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China; Department of Laboratory Medicine, Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States; Claritas Genomics, Cambridge, MA, United States. Electronic address: yiping.shen@childrens.harvard.edu.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
mesh_terms: D001483:Base Sequence; D002681:China; D003409:Congenital Hypothyroidism / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D017354:Point Mutation; D017384:Sequence Deletion; D013954:Thyroglobulin / Q000235:genetics*
chemical_list: D013954:Thyroglobulin
keywords: Congenital hypothyroidism; Genetic screening; Thyroglobulin gene; Variants interpretation