Send to

Choose Destination
Oncotarget. 2017 Jan 31;8(5):8707-8716. doi: 10.18632/oncotarget.14419.

Identification and characterization of novel PAX8 mutations in Congenital Hypothyroidism(CH) in a Chinese population.

Liu S1,2, Wang X3,4, Zou H5, Ge Y3, Wang F6, Wang Y6, Yan S6, Xia H4,7,8, Xing M6,9.

Author information

Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, China.
Genetic Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Biochemistry and Molecular Biology, School of Medicine, Qingdao University, Qingdao, China.
National Research Institute for Family Planning, Beijing, China.
Neonatal Screening Center, Jinan Women & Children Medical Healthcare Center, Jinan, China.
Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Graduate School, Peking Union Medical College, Beijing, China.
World Health Organization Collaborating Centre for Research in Human Reproduction, Beijing, China.
Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine, USA.



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.


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).


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.


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.


PAX8 mutation; congenital hypothyroidism; paired box transcription factor; thyroid dysgenesis; thyroid gene

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center