Identification and characterization of novel PAX8 mutations in congenital hypothyroidism (CH) in a Chinese population

Shiguo Liu, Xueqin Wang, Hui Zou, Yinlin Ge, Fang Wang, Yangang Wang, Shengli Yan, Hongfei Xia, Mingzhao Xing

Research output: Contribution to journalArticlepeer-review


Objective: Based on mutations in PAX8 is associated with thyroid dysgenesis. We aim to identify and characterize PAX8 mutations in a large cohort of congenital hypothyroidism(CH) from thyroid dysgenesis in Chinese population. Methods: We screened 453 unrelated Chinese patients with CH from thyroid dysgenesis for PAX8 mutations by sequencing the whole coding regions of PAX8 on genomic DNA isolated from blood. Cell transfection assays using various vector constructs and induced mutagenesis as well as electrophoretic mobility shift assays were used to investigate the effects of selected mutations on the transcribing and binding activities of PAX8 at the promoters of target genes for thyroglobulin (TG) and thyroperoxidase (TPO). Results: Five PAX8 mutations were found, yielding a mutation prevalence of 5/453 (1.1%). We selected two mutations in the critical paired domain of PAX8 and generated mutants D94N and G41V. We demonstrated G41V was unable to bind the specific sequence in the promoters of TG and TPO and activate them. D94N could bind to TG and TPO promoters and normally activate the TG promoter transcription but not the TPO promoter transcription. We also demonstrated a dominant negative role of the PAX8 mutants in impairing the function of the wild-type PAX8. Conclusion: We for the first time documented the prevalence and characterized the function of PAX8 mutations in CH in Chinese population. The study specifically demonstrated the role of novel mutations D94N and G41V in impairing the function of PAX8, providing further evidence for genetic PAX8 defects as a disease mechanism in CH.

Original languageEnglish (US)
Pages (from-to)8707-8716
Number of pages10
Issue number5
StatePublished - Jan 2 2017
Externally publishedYes


  • Congenital hypothyroidism
  • Paired box transcription factor
  • PAX8 mutation
  • Thyroid dysgenesis
  • Thyroid gene

ASJC Scopus subject areas

  • Oncology


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