ArticleEuropean journal of endocrinology2021
The phenotypic spectrum associated with OTX2 mutations in humans.
Article in European journal of endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Re-analysis of gene mutations found in pituitary stalk interruption syndrome and a new hypothesis on the etiology.Frontiers in endocrinology · 2024Pooled it
- Genomic Profiling of Anophthalmia/Microphthalmia-Associated CNVs Reveals Complex Genotype-Phenotype Correlations and Incomplete Penetrance.Molecular genetics & genomic medicine · 2026Article
- Review
- Analysis ofInternational journal of molecular sciences · 2025Article
- Maternal factor OTX2 regulates human embryonic genome activation and early development.Nature genetics · 2025Article
- Hypopituitarism: genetic, developmental, and acquired etiologies with a focus on the emerging concept of autoimmune hypophysitis.Endocrine journal · 2025Review
- Beyond CHD7 gene: unveiling genetic diversity in clinically suspected CHARGE syndrome.Journal of human genetics · 2025Article
- Article
- Human-based complexFrontiers in cell and developmental biology · 2025Review
- The molecular basis of hypoprolactinaemia.Reviews in endocrine & metabolic disorders · 2024Review
- Non-syndromic OTX2-associated pattern dystrophy: a 10-year multimodal imaging study.Documenta ophthalmologica. Advances in ophthalmology · 2024Article
- Article
- Article
- The Emerging Roles of the Cephalic Neural Crest in Brain Development and Developmental Encephalopathies.International journal of molecular sciences · 2023Review
- c-Jun N-terminal kinase 1 (JNK1) phosphorylates OTX2 transcription factor that regulates early retinal development.Genes & genomics · 2023Article
- Disease-causing mutations in genes encoding transcription factors critical for photoreceptor development.Frontiers in molecular neuroscience · 2023Review
- Transcription factors in microcephaly.Frontiers in neuroscience · 2023Review
- Presentation and diagnosis of childhood-onset combined pituitary hormone deficiency: A single center experience from over 30 years.EClinicalMedicine · 2022Article
- Genetic heterogeneity in corpus callosum agenesis.Frontiers in genetics · 2022Review
- Advances in differential diagnosis and management of growth hormone deficiency in children.Nature reviews. Endocrinology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 5 institutions in 4 countries.
Funding
Abstract
Objective: The transcription factor OTX2 is implicated in ocular, craniofacial, and pituitary development. Design: We aimed to establish the contribution of OTX2 mutations in congenital hypopituitarism patients with/without eye abnormalities, study functional consequences, and establish OTX2 expression in the human brain, with a view to investigate the mechanism of action. Methods: We screened patients from the UK (n = 103), international centres (n = 24), and Brazil (n = 282); 145 were within the septo-optic dysplasia spectrum, and 264 had no eye phenotype. Transactivation ability of OTX2 variants was analysed in murine hypothalamic GT1-7 neurons. In situ hybridization was performed on human embryonic brain sections. Genetically engineered mice were generated with a series of C-terminal OTX2 variants. Results: Two chromosomal deletions and six haploinsufficient mutations were identified in individuals with eye abnormalities; an affected relative of one patient harboured the same mutation without an ocular phenotype. OTX2 truncations led to significant transactivation reduction. A missense variant was identified in another patient without eye abnormalities; however, studies revealed it was most likely not causative. In the mouse, truncations proximal to aa219 caused anophthalmia, while distal truncations and the missense variant were tolerated. During human embryogenesis, OTX2 was expressed in the posterior pituitary, retina, ear, thalamus, choroid plexus, and partially in the hypothalamus, but not in the anterior pituitary. Conclusions: OTX2 mutations are rarely associated with hypopituitarism in isolation without eye abnormalities, and may be variably penetrant, even within the same pedigree. Our data suggest that the endocrine phenotypes in patients with OTX2 mutations are of hypothalamic origin.
Indexed as
Identifiers
What OpenQuestion holds
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.