ArticleThyroid : official journal of the American Thyroid Association2013
Two cases of thyroid dysgenesis caused by different novel PAX8 mutations in the DNA-binding region: in vitro studies reveal different pathogenic mechanisms.
Article in Thyroid : official journal of the American Thyroid Association, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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13 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- The molecular causes of thyroid dysgenesis: a systematic review.Journal of endocrinological investigation · 2013Pooled it
- A case of syndromic congenital hypothyroidism with a 15.2 Mb interstitial deletion on 2q12.3q14.2 involvingClinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2023Article
- PAX8 in the Junction between Development and Tumorigenesis.International journal of molecular sciences · 2022Review
- Functional analysis ofClinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2022Article
- A patient with congenital hypothyroidism due to aClinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2022Article
- Pax2 and Pax8 Proteins Regulate Urea Transporters and Aquaporins to Control Urine Concentration in the Adult Kidney.Journal of the American Society of Nephrology : JASN · 2020Article
- Identification and functional characterization of a novelClinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2020Article
- The incidence of congenital hypothyroidism (CH) in Guangxi, China and the predictors of permanent and transient CH.Endocrine connections · 2017Article
- Resistance to thyrotropin.Best practice & research. Clinical endocrinology & metabolism · 2017Review
- Identification and characterization of novel PAX8 mutations in Congenital Hypothyroidism(CH) in a Chinese population.Oncotarget · 2017Article
- Mutation screening of the TPO gene in a cohort of 192 Chinese patients with congenital hypothyroidism.BMJ open · 2016Article
- Mutation screening of DUOX2 in Chinese patients with congenital hypothyroidism.Journal of endocrinological investigation · 2015Article
- A De novo PAX8 mutation in a Chinese child with congenital thyroid dysgenesis.International journal of clinical and experimental pathology · 2015Article
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7 authors at 2 institutions in 2 countries.
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Abstract
backgroundMutations in PAX8, a transcription factor gene, cause thyroid dysgenesis (TD). The extreme variability of the thyroid phenotype makes it difficult to identify individuals harboring PAX8 gene mutations. Here we describe two patients with TD and report two novel PAX8 gene mutations (S54R and R133Q). We performed in vitro studies to functionally characterize these mutations.
methodsUsing PAX8 expression vectors, we investigated whether the PAX8 mutants localized correctly to the nucleus. To analyze the DNA-binding properties of S54R and R133Q, electrophoretic mobility shift assays were performed. Furthermore, we measured whether the mutant PAX8 proteins were able to activate the thyroglobulin (TG)- and the thyroperoxidase (TPO)-promoters.
resultsS54R had an impaired binding to DNA and a negligible activity on the TG- and the TPO-promoters. The DNA-binding property of R133Q, which is located in the highly conserved terminal portion of the PAX8 DNA-binding domain, was normal. Interestingly, it also exhibited dramatically impaired activation of the TG- and TPO-promoters. However, R133Q has no dominant negative effect on the WT protein in vitro. Thus, the underlying molecular mechanism by which the function of R133Q is impaired remains to be elucidated.
conclusionsWe identified and functionally characterized two novel mutations of the PAX8 gene that lead to TD by distinct mechanisms. A structural defect of the mutant R133Q leading to a reduced capability for induced fit upon DNA interaction might explain the disparity between its apparently normal binding to DNA, but lack of promoter activation.
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