ArticleThe Journal of clinical investigation2002
Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 3 of them syntheses that pooled it.
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Who cites it
70 citing papers in PubMed, 3 syntheses or guidelines pooled it, 179 citations in OpenAlex.
- Respiratory and other organ manifestations inFrontiers in medicine · 2025Pooled it
- European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism.The Journal of clinical endocrinology and metabolism · 2014Guideline
- The molecular causes of thyroid dysgenesis: a systematic review.Journal of endocrinological investigation · 2013Pooled it
- Article
- Resolving thyroid lineage cell trajectories merging into a dual endocrine gland in mammals.Nature communications · 2026Article
- Genetics of primary congenital hypothyroidism: three decades of discoveries and persisting etiological challenges.European thyroid journal · 2025Review
- Brain Abnormalities in Young Single- and Double-Heterozygote Mice for Both Nkx2-1- and Pax8-Null Mutations.Molecular neurobiology · 2025Article
- The transcription regulator Lmo3 is required for the development of medial ganglionic eminence derived neurons in the external globus pallidus.Developmental biology · 2023Article
- Tissue specificity of oncogenic BRAF targeted to lung and thyroid through a shared lineage factor.iScience · 2023Article
- Novel Missense Variants inInternational journal of molecular sciences · 2023Article
- Whole-Exome Sequencing in Congenital Hypothyroidism Due to Thyroid Dysgenesis.Thyroid : official journal of the American Thyroid Association · 2022Article
- Altered pituitary morphology as a sign of benign hereditary chorea caused by TITF1/NKX2.1 mutations.Neurogenetics · 2022Article
- Deciphering an isolated lung phenotype of NKX2-1 frameshift pathogenic variant.Frontiers in pediatrics · 2022Article
- Genetics of primary congenital hypothyroidism-a review.Hormones (Athens, Greece) · 2021Review
- Deletion of conserved non-coding sequences downstream from NKX2-1: A novel disease-causing mechanism for benign hereditary chorea.Molecular genetics & genomic medicine · 2021Article
- Two distinct E3 ligases, SCFFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Genetic causes of surfactant protein abnormalities.Current opinion in pediatrics · 2019Review
- Mutations in the thyroid transcription factor gene NKX2-1 result in decreased expression of SFTPB and SFTPC.Pediatric research · 2018Article
- Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis.Archives of endocrinology and metabolism · 2018Article
- NFE2-Related Transcription Factor 2 Coordinates Antioxidant Defense with Thyroglobulin Production and Iodination in the Thyroid Gland.Thyroid : official journal of the American Thyroid Association · 2018Article
10 more citing papers are in PubMed but not listed here.
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10 authors at 4 institutions in 2 countries.
Funding
Abstract
Three genes, TTF1, TTF2, and PAX8, involved in thyroid gland development and migration have been identified. Yet systematic screening for defects in these genes in thyroid dysgenesis gave essentially negative results. In particular, no TTF1 gene defects were found in 76 individuals with thyroid dysgenesis even though a deletion of this gene in the mouse results in thyroid and lung agenesis and defective diencephalon. We report a 6-year-old boy with predominant dyskinesia, neonatal respiratory distress, and mild hyperthyrotropinemia. One allele of his TTF1 gene had a guanidine inserted into codon 86 producing a nonsense protein of 407, rather than 371, amino acids. The mutant TTF1 did not bind to its canonical cis-element or transactivate a reporter gene driven by the thyroglobulin promoter, a natural target of TTF1. Failure of the mutant TTF1 to interfere with binding and transactivation functions of the wild-type TTF1 suggested that the syndrome was caused by haploinsufficiency. This was confirmed in mice heterozygous for Ttf1 gene deletion, heretofore considered to be normal. Compared with wild-type littermates, Ttf1(+/-) mice had poor coordination and a significant elevation of serum thyrotropin. Therefore, haploinsufficiency of the TTF1 gene results in a predominantly neurological phenotype and secondary hyperthyrotropinemia.
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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.