ArticlePloS one2012
The ambiguous role of NKX2-5 mutations in thyroid dysgenesis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- [Clinical guideline of «congenital hypothyroidism»].Problemy endokrinologii · 2022Guideline
- The molecular causes of thyroid dysgenesis: a systematic review.Journal of endocrinological investigation · 2013Pooled it
- Molecular Genetics of Primary Congenital Hypothyroidism: Established and Emerging Contributors to Thyroid Dysgenesis.International journal of molecular sciences · 2025Review
- Functional mutations in the thyroid-stimulating hormone receptor in natural stickleback populations at sites identical to human disease-causing mutations.BMC ecology and evolution · 2025Article
- Revealing the genotype-phenotype correlations of congenital hypothyroidism in Yunnan Province, Southwest China.Frontiers in endocrinology · 2025Article
- NKX2-5 Variant in Two Siblings with Thyroid Hemiagenesis.International journal of molecular sciences · 2022Article
- Genetics of primary congenital hypothyroidism-a review.Hormones (Athens, Greece) · 2021Review
- Further Evidence That Defects in Main Thyroid Dysgenesis-Related Genes Are an Uncommon Etiology for Primary Congenital Hypothyroidism in Mexican Patients: Report of Rare Variants inChildren (Basel, Switzerland) · 2021Article
- Crystal Structures of Ternary Complexes of MEF2 and NKX2-5 Bound to DNA Reveal a Disease Related Protein-Protein Interaction Interface.Journal of molecular biology · 2020Article
- Systems Biology Approaches to Investigate Genetic and Epigenetic Molecular Progression Mechanisms for Identifying Gene Expression Signatures in Papillary Thyroid Cancer.International journal of molecular sciences · 2019Article
- Clinical course of infants with congenital heart disease who developed thyroid dysfunction within 100 days.Annals of pediatric endocrinology & metabolism · 2017Article
- Congenital hypothyroidism: insights into pathogenesis and treatment.International journal of pediatric endocrinology · 2017Review
- Nkx2-5 Is Expressed in Atherosclerotic Plaques and Attenuates Development of Atherosclerosis in Apolipoprotein E-Deficient Mice.Journal of the American Heart Association · 2016Article
- Article
- Submental thyroid ectopy might cause subclinical hypothyroidism in early childhood.SAGE open medical case reports · 2016Article
- Sublingual thyroid ectopy: similarities and differences with Kallmann syndrome.F1000prime reports · 2015Review
- Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NKX2-5 is a homeodomain-containing transcription factor implied in both heart and thyroid development. Numerous mutations in NKX2-5 have been reported in individuals with congenital heart disease (CHD), but recently a select few have been associated with thyroid dysgenesis, among which the p.A119S variation. We sequenced NKX2-5 in 303 sporadic CHD patients and 38 families with at least two individuals with CHD. The p.A119S variation was identified in two unrelated patients: one was found in the proband of a family with four affected individuals with CHD and the other in a sporadic CHD patient. Clinical evaluation of heart and thyroid showed that the mutation did not segregate with CHD in the familial case, nor did any of the seven mutation carriers have thyroid abnormalities. We tested the functional consequences of the p.A119S variation in a cellular context by performing transactivation assays with promoters relevant for both heart and thyroid development in rat heart derived H10 cells and HELA cells. There was no difference between wildtype NKX2-5 and p.A119S NKX2-5 in activation of the investigated promoters in both cell lines. Additionally, we reviewed the current literature on the topic, showing that there is no clear evidence for a major pathogenic role of NKX2-5 mutations in thyroid dysgenesis. In conclusion, our study demonstrates that p.A119S does not cause CHD or TD and that it is a rare variation that behaves equal to wildtype NKX2-5. Furthermore, given the wealth of published evidence, we suggest that NKX2-5 mutations do not play a major pathogenic role in thyroid dysgenesis, and that genetic testing of NKX2-5 in TD is not warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.