ArticlePloS one2012
Gradual loss of ACTH due to a novel mutation in LHX4: comprehensive mutation screening in Japanese patients with congenital hypopituitarism.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 32 citations in OpenAlex.
- A Novel Missense Variant inChildren (Basel, Switzerland) · 2025Article
- A Pedigree WithClinical case reports · 2025Article
- Central Adrenal Insufficiency: Etiology and Diagnostic ApproachJournal of clinical research in pediatric endocrinology · 2025Review
- Clinical and genetic features of childhood-onset congenital combined pituitary hormone deficiency: a retrospective, single-center cohort study.Annals of pediatric endocrinology & metabolism · 2024Article
- Article
- Congenital Hypopituitarism During the Neonatal Period: Epidemiology, Pathogenesis, Therapeutic Options, and Outcome.Frontiers in pediatrics · 2020Review
- Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era.Endocrine reviews · 2016Review
- Novel Lethal Form of Congenital Hypopituitarism Associated With the First Recessive LHX4 Mutation.The Journal of clinical endocrinology and metabolism · 2015Article
- Identifying the Deleterious Effect of Rare LHX4 Allelic Variants, a Challenging Issue.PloS one · 2015Article
- Molecular and Clinical Findings in Patients with LHX4 and OTX2 Mutations.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2013Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in transcription factors genes, which are well regulated spatially and temporally in the pituitary gland, result in congenital hypopituitarism (CH) in humans. The prevalence of CH attributable to transcription factor mutations appears to be rare and varies among populations.This study aimed to define the prevalence of CH in terms of nine CH-associated genes among Japanese patients. We enrolled 91 Japanese CH patients for DNA sequencing of POU1F1, PROP1, HESX1, LHX3, LHX4, SOX2, SOX3, OTX2, and GLI2. Additionally, gene copy numbers for POU1F1, PROP1, HESX1, LHX3, and LHX4 were examined by multiplex ligation-dependent probe amplification. The gene regulatory properties of mutant LHX4 proteins were characterized in vitro. We identified two novel heterozygous LHX4 mutations, namely c.249-1G>A, p.V75I, and one common POU1F1 mutation, p.R271W. The patient harboring the c.249-1G>A mutation exhibited isolated growth hormone deficiency at diagnosis and a gradual loss of ACTH, whereas the patient with the p.V75I mutation exhibited multiple pituitary hormone deficiency. In vitro experiments showed that both LHX4 mutations were associated with an impairment of the transactivation capacities of POU1F1 andαGSU, without any dominant-negative effects. The total mutation prevalence in Japanese CH patients was 3.3%. This study is the first to describe, a gradual loss of ACTH in a patient carrying an LHX4 mutation. Careful monitoring of hypothalamic-pituitary -adrenal function is recommended for CH patients with LHX4 mutations.
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