ArticleClinical endocrinology2018
A novel IGSF1 mutation in a large Irish kindred highlights the need for familial screening in the IGSF1 deficiency syndrome.
Article in Clinical endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Retrospective, multicentre evaluation of central congenital hypothyroidism in the UK.European thyroid journal · 2026Article
- Identification of a Novel Nonsense Mutation in theChildren (Basel, Switzerland) · 2025Article
- A Novel De Novo Nonsense Pathogenic Variant inJCEM case reports · 2025Article
- Insights Into Central Congenital Hypothyroidism: A Multicenter Retrospective Analysis.The Journal of clinical endocrinology and metabolism · 2025Article
- The molecular basis of hypoprolactinaemia.Reviews in endocrine & metabolic disorders · 2024Review
- 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
- Thyroid Stimulating Hormone and Thyroid Hormones (Triiodothyronine and Thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status.Thyroid : official journal of the American Thyroid Association · 2023Review
- Hepatomegaly and fatty liver disease secondary to central hypothyroidism in combination with macrosomia as initial presentation of IGSF1 deficiency syndrome.Hormones (Athens, Greece) · 2023Review
- Intrinsic sexual dimorphism in the placenta determines the differential response to benzene exposure.iScience · 2023Article
- Article
- The IGSF1 Deficiency Syndrome May Present with Normal Free T4 Levels, Severe Obesity, or Premature Testicular GrowthJournal of clinical research in pediatric endocrinology · 2021Article
- Hypoprolactinemia as a Clue to Diagnosis of Mild Central Hypothyroidism due toJournal of clinical research in pediatric endocrinology · 2020Article
- Response to Letter to the Editor: "IGSF1 Deficiency Results in Human and Murine Somatotrope Neurosecretory Hyperfunction".The Journal of clinical endocrinology and metabolism · 2020Article
- IGSF1 Deficiency Results in Human and Murine Somatotrope Neurosecretory Hyperfunction.The Journal of clinical endocrinology and metabolism · 2020Article
- Article
- The diagnosis and management of central hypothyroidism in 2018.Endocrine connections · 2019Review
- Recent advances in research on isolated congenital central hypothyroidism.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2019Article
- A novel IGSF1 mutation in a large Irish kindred highlights the need for familial screening in the IGSF1 deficiency syndrome.Clinical endocrinology · 2018Article
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Authors and funding
16 authors at 8 institutions in 5 countries.
Funding
Abstract
objectiveLoss-of-function mutations in IGSF1 result in X-linked central congenital hypothyroidism (CeCH), occurring in isolation or associated with additional pituitary hormone deficits. Intrafamilial penetrance is highly variable and a minority of heterozygous females are also affected. We identified and characterized a novel IGSF1 mutation and investigated its associated phenotypes in a large Irish kindred. DESIGN, PATIENTS AND MEASUREMENTS: A novel hemizygous IGSF1 mutation was identified by direct sequencing in two brothers with CeCH, and its functional consequences were characterized in vitro. Genotype-phenotype correlations were investigated in the wider kindred.
resultsThe mutant IGSF1 protein (c.2318T > C, p.L773P) exhibited decreased plasma membrane expression in vitro due to impaired trafficking from the endoplasmic reticulum. Ten hemizygous males and 11 heterozygous females exhibited characteristic endocrine deficits. Ireland operates a TSH-based CH screening programme, which does not detect CeCH; therefore, genetic ascertainment preceded biochemical diagnosis of moderate CH in five of seven boys as well as their 75-year-old grandfather. Clinical features potentially attributable to hypothyroidism were variable; normal free T3 (FT3) and low/low normal reverse T3 (rT3) concentrations suggested that preferential deiodination of FT4 to FT3 may help maintain tissue euthyroidism in some individuals. However, neonatal jaundice, delayed speech or growth, and obesity were observed in seven subjects in whom diagnosis was delayed.
conclusionsAs observed with other IGSF1 mutations, p.L773P results in variably penetrant IGSF1 deficiency syndrome. Our observations emphasize the need for multi-generation genetic ascertainment in affected families, especially where TSH-based CH screening programmes may fail to detect CeCH at birth.
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