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Mol Cell Endocrinol. 2016 Mar 5;423:60-6. doi: 10.1016/j.mce.2016.01.007. Epub 2016 Jan 8.

Thyroglobulin gene mutations in Chinese patients with congenital hypothyroidism.

Author information

1
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.
2
Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
3
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
4
Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China. Electronic address: chenshaoke123@163.com.
5
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.

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.

KEYWORDS:

Congenital hypothyroidism; Genetic screening; Thyroglobulin gene; Variants interpretation

PMID:
26777470
DOI:
10.1016/j.mce.2016.01.007
[Indexed for MEDLINE]

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