ArticleEndocrinology2015
Functional zebrafish studies based on human genotyping point to netrin-1 as a link between aberrant cardiovascular development and thyroid dysgenesis.
Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- 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
- Approach to the patient: genetics and management of congenital hypothyroidism.The Journal of clinical endocrinology and metabolism · 2026Article
- A disrupted compartment boundary underlies abnormal cardiac patterning and congenital heart defects.Nature cardiovascular research · 2026Article
- Expression of Netrin-1 in the developing mouse heart.Gene expression patterns : GEP · 2025Article
- Molecular Genetics of Primary Congenital Hypothyroidism: Established and Emerging Contributors to Thyroid Dysgenesis.International journal of molecular sciences · 2025Review
- In Vivo Models of Cardiovascular Disease:Biomedicines · 2025Review
- Genetics of primary congenital hypothyroidism: three decades of discoveries and persisting etiological challenges.European thyroid journal · 2025Review
- A Novel De Novo Missense Variant in Netrin-1 (NTN1) Associated With Chorioretinal Coloboma, Sensorineural Hearing Loss and Polydactyly.Clinical genetics · 2025Article
- Comprehensive pan-cancer analysis reveals NTN1 as an immune infiltrate risk factor and its potential prognostic value in SKCM.Scientific reports · 2025Article
- Genetic and Environmental Factors in Autoimmune Thyroid Disease: Exploring Associations with Selenium Levels and Novel Loci in a Latvian Cohort.Current issues in molecular biology · 2024Article
- GWAS of thyroid dysgenesis identifies a risk locus at 2q33.3 linked to regulation of Wnt signaling.Human molecular genetics · 2022Article
- Genetics of congenital hypothyroidism: Modern concepts.Pediatric investigation · 2022Review
- Whole-Exome Sequencing in Congenital Hypothyroidism Due to Thyroid Dysgenesis.Thyroid : official journal of the American Thyroid Association · 2022Article
- Genetics of primary congenital hypothyroidism-a review.Hormones (Athens, Greece) · 2021Review
- New genetics in congenital hypothyroidism.Endocrine · 2021Review
- TUBB1 mutations cause thyroid dysgenesis associated with abnormal platelet physiology.EMBO molecular medicine · 2018Article
- The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes.European journal of endocrinology · 2018Article
- How zebrafish research has helped in understanding thyroid diseases.F1000Research · 2017Review
- Sublingual thyroid ectopy: similarities and differences with Kallmann syndrome.F1000prime reports · 2015Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Congenital hypothyroidism caused by thyroid dysgenesis (CHTD) is a common congenital disorder with a birth prevalence of 1 case in 4000 live births, and up to 8% of individuals with CHTD have co-occurring congenital heart disease. Initially we found nine patients with cardiac and thyroid congenital disorders in our cohort of 158 CHTD patients. To enrich for a rare phenotype likely to be genetically simpler, we selected three patients with a ventricular septal defect for molecular studies. Then, to assess whether rare de novo copy number variants and coding mutations in candidate genes are a source of genetic susceptibility, we used a genome-wide single-nucleotide polymorphism array and Sanger sequencing to analyze blood DNA samples from selected patients with co-occurring CHTD a congenital heart disease. We found rare variants in all three patients, and we selected Netrin-1 as the biologically most plausible contributory factor for functional studies. In zebrafish, ntn1a and ntn1b were not expressed in thyroid tissue, but ntn1a was expressed in pharyngeal arch mesenchyme, and ntn1a-deficient embryos displayed defective aortic arch artery formation and abnormal thyroid morphogenesis. The functional activity of the thyroid in ntn1a-deficient larvae was, however, preserved. Phenotypic analysis of affected zebrafish indicates that abnormal thyroid morphogenesis resulted from a lack of proper guidance exerted by the dysplastic vasculature of ntn1a-deficient embryos. Hence, careful phenotyping of patients combined with molecular and functional studies in zebrafish identify Netrin-1 as a potential shared genetic factor for cardiac and thyroid congenital defects.
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