ArticleThe Journal of clinical investigation2002
Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency.
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 118 papers, 6 of them syntheses that pooled it.
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Who cites it
118 citing papers in PubMed, 6 syntheses or guidelines pooled it, 311 citations in OpenAlex.
- Respiratory and other organ manifestations inFrontiers in medicine · 2025Pooled it
- Systematic review of thyroid function in NKX2-1-related disorders: Treatment and follow-up.PloS one · 2024Pooled it
- Systematic review of thyroid function in NKX2-1-related disorders: Screening and diagnosis.PloS one · 2024Pooled it
- Congenital Hypothyroidism: A 2020-2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology.Thyroid : official journal of the American Thyroid Association · 2021Guideline
- 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
- Crystal structure of the NKX2-1 homeodomain bound to a palindromic DNA recognition sequence.Acta crystallographica. Section F, Structural biology communications · 2026Article
- Roles of External Factors and Polygenic Susceptibility in Thyroid Nodules and Goiter Among Children Aged 8-10 Years in Iodine-adequate Areas of Northern China.Biological trace element research · 2026Article
- Approach to the patient: genetics and management of congenital hypothyroidism.The Journal of clinical endocrinology and metabolism · 2026Article
- Resolving thyroid lineage cell trajectories merging into a dual endocrine gland in mammals.Nature communications · 2026Article
- Genetic Analyses in a Cohort of Pediatric Patients with Congenital Hypothyroidism Based on Congenital Hypothyroidism Consensus Guideline.Hormone research in paediatrics · 2026Article
- LIN28-mediated gene regulatory loops synchronize transitions throughout organogenesis.Biochemistry and biophysics reports · 2025Article
- Congenital hypothyroidism in two children affected by Sotos syndrome: a simple association?Italian journal of pediatrics · 2025Article
- Amplified dosage of the NKX2-1 lineage transcription factor controls its oncogenic role in lung adenocarcinoma.Molecular cell · 2025Article
- 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
- Insights on the Shared Genetic Landscape of Neurodevelopmental and Movement Disorders.Current neurology and neuroscience reports · 2025Review
- Interstitial lung disease in the newborn.Journal of perinatology : official journal of the California Perinatal Association · 2025Review
- Innovations in Childhood Interstitial and Diffuse Lung Disease.Clinics in chest medicine · 2024Review
58 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The occurrence of neurological symptoms and developmental delay in patients affected by congenital hypothyroidism (CH) has been attributed to the lack of thyroid hormone in the developing CNS. Accordingly, after the introduction of neonatal screening programs for CH, which allowed early and adequate treatment, an almost normal outcome for most CH patients could be achieved. However, a few patients did not reach this favorable outcome despite early and adequate treatment. Here we describe five patients with variable degrees of CH who suffered from choreoathetosis, muscular hypotonia, and pulmonary problems, an association of symptoms that had not been described before this study. Since this clinical picture matched the phenotype of mice targeted for deletion of the transcription factor gene Nkx2-1, we investigated the human NKX2-1 gene in these five patients. We found heterozygous loss of function mutations in each of these five patients, e.g., one complete gene deletion, one missense mutation (G2626T), and three nonsense mutations (2595insGG, C2519A, C1302A). Therefore, the unfavorable outcome in patients with CH, especially those with choreoathetosis and pulmonary symptoms, can be explained by mutations in the NKX2-1 gene rather than by hypothyroidism. Moreover, the association of symptoms in the patients with NKX2-1 mutations points to an important role of human NKX2-1 in the development and function of thyroid, basal ganglia, and lung, as already described for rodents.
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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.