Thyroglobulin gene mutations in Chinese patients with congenital hypothyroidism. (5th March 2016)

• Record Type: Journal Article
• Authors: Hu, Xuyun; Chen, Rongyu; Fu, Chunyun; Fan, Xin; Wang, Jin; Qian, Jiale; Yi, Shang; Li, Chuan; Luo, Jingsi; Su, Jiasun; Zhang, Shujie; Xie, Bobo; Zheng, Haiyang; Lai, Yunli; Chen, Yun; Li, Hongdou; Gu, Xuefan; Chen, Shaoke; Shen, Yiping
• Is Part Of: Molecular and cellular endocrinology. Volume 423(2016)
• Page Start: 60
• Page End: 66
• Publication Date: 2016-03-05
• Subjects: Congenital hypothyroidism -- Thyroglobulin gene -- Genetic screening -- Variants interpretation; TG thyroglobulin -- CH congenital hypothyroidism -- PCH permanent congenital hypothyroidism -- VUS variants of unknown significance -- ACHE acetylcholinesterase -- TSH thyroid stimulating hormone -- FT3 free triiodothyronine -- FT4 free tetraiodothyronine -- TT3 total triiodothyronine -- TT4 total tetraiodothyronine -- HGMD Human Gene Mutation Database -- ExAC Exome Aggregation Consortium -- EVS Exome Variant Server; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2016.01.007
• Languages: English
• ISSNs: 0303-7207

Abstract

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. Highlights: First TG mutation screening among Chinese CH patients were conducted. Chinese ethnicity specific TG mutation spectrum and frequency were uncovered. Four novel and a recurrent, Chinese-specific pathogenic TG variants were uncovered. Clinical significants of 22 TG variants were classified according to new guidelines. Clinical phenotypes of patients with TG variants were elaborated.