ArticleNature genetics2012
Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement.
Article in Nature genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 2 of them syntheses that pooled it.
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Who cites it
94 citing papers in PubMed, 2 syntheses or guidelines pooled it, 215 citations in OpenAlex.
- "Management of andrological disorders from childhood and adolescence to transition age: guidelines from the Italian Society of Andrology and Sexual Medicine (SIAMS) in collaboration with the Italian Society for Pediatric Endocrinology and Diabetology (SIEDP)-Part-1".Journal of endocrinological investigation · 2025Guideline
- 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
- X chromosome-wide association studies for quantitative trait loci based on the mixture of general pedigrees and additional unrelated individuals.Briefings in bioinformatics · 2026Article
- Xq26.2 Contiguous Gene Deletion InvolvingGenes · 2026Article
- Identification of a NovelJournal of clinical research in pediatric endocrinology · 2026Article
- Identification of a Novel Nonsense Mutation in theChildren (Basel, Switzerland) · 2025Article
- Diagnostic Challenges of Short Stature and Growth Hormone Insufficiency Across Different Genetic Etiologies.Biomedicines · 2025Review
- Hypopituitarism: genetic, developmental, and acquired etiologies with a focus on the emerging concept of autoimmune hypophysitis.Endocrine journal · 2025Review
- A Novel De Novo Nonsense Pathogenic Variant inJCEM case reports · 2025Article
- Newborn screening for central congenital hypothyroidism: past, present and future.European thyroid journal · 2025Review
- The molecular basis of hypoprolactinaemia.Reviews in endocrine & metabolic disorders · 2024Review
- Deciphering the mystery of CHNG3.Annals of pediatric endocrinology & metabolism · 2024Article
- Disturbed function of TBL1X has a differential effect on T3-regulated gene expression in two human liver cell models.European thyroid journal · 2024Article
- Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation.Nature communications · 2024Article
- Hypothalamic hormone deficiency enables physiological anorexia.bioRxiv : the preprint server for biology · 2024Article
- The hypothalamic-pituitary-thyroid axis is intact in male insulin receptor substrate 4 knockout mice.European thyroid journal · 2024Article
- A novel variant ofClinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2024Article
- A Novel Pathogenic IGSF1 Variant in a Patient with GH and TSH Deficiency Diagnosed by HighJournal of clinical research in pediatric endocrinology · 2023Article
- Hepatomegaly and fatty liver disease secondary to central hypothyroidism in combination with macrosomia as initial presentation of IGSF1 deficiency syndrome.Hormones (Athens, Greece) · 2023Review
- Neonatal screening for primary and central congenital hypothyroidism: is it time to go Dutch?European thyroid journal · 2023Review
34 more citing papers are in PubMed but not listed here.
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Authors and funding
41 authors at 16 institutions in 5 countries.
Funding
Abstract
Congenital central hypothyroidism occurs either in isolation or in conjunction with other pituitary hormone deficits. Using exome and candidate gene sequencing, we identified 8 distinct mutations and 2 deletions in IGSF1 in males from 11 unrelated families with central hypothyroidism, testicular enlargement and variably low prolactin concentrations. IGSF1 is a membrane glycoprotein that is highly expressed in the anterior pituitary gland, and the identified mutations impair its trafficking to the cell surface in heterologous cells. Igsf1-deficient male mice show diminished pituitary and serum thyroid-stimulating hormone (TSH) concentrations, reduced pituitary thyrotropin-releasing hormone (TRH) receptor expression, decreased triiodothyronine concentrations and increased body mass. Collectively, our observations delineate a new X-linked disorder in which loss-of-function mutations in IGSF1 cause central hypothyroidism, likely secondary to an associated impairment in pituitary TRH signaling.
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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.