ArticleHuman molecular genetics2023
Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man.
Article in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 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
- Detection of theAnimals : an open access journal from MDPI · 2026Article
- The Transcription Factors Six3 and Six6 in Neuromedin-S Neurons Differentially Affect Circadian Rhythms.Journal of neuroscience research · 2026Article
- Recent advances in the diagnosis and molecular pathogenesis of holoprosencephaly: a review.Journal of applied genetics · 2025Article
- Hypopituitarism: genetic, developmental, and acquired etiologies with a focus on the emerging concept of autoimmune hypophysitis.Endocrine journal · 2025Review
- Nucleoredoxin regulates WNT signaling during pituitary stem cell differentiation.Human molecular genetics · 2025Article
- Nucleoredoxin regulates WNT signaling during pituitary stem cell differentiation.bioRxiv : the preprint server for biology · 2025Article
- Long Noncoding RNAs Expressed in Mouse Pituitary Development and Mature Hormone-Producing Cells.Endocrinology · 2024Article
- The homeodomain transcription factor Six3 regulates hypothalamic Pomc expression and its absence from POMC neurons induces hyperphagia and mild obesity in male mice.Molecular metabolism · 2024Article
- Impact of Sonic Hedgehog-dependent sphenoid bone defect on craniofacial growth.Clinical and experimental dental research · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
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Abstract
Congenital hypopituitarism is a genetically heterogeneous condition that is part of a spectrum disorder that can include holoprosencephaly. Heterozygous mutations in SIX3 cause variable holoprosencephaly in humans and mice. We identified two children with neonatal hypopituitarism and thin pituitary stalk who were doubly heterozygous for rare, likely deleterious variants in the transcription factors SIX3 and POU1F1. We used genetically engineered mice to understand the disease pathophysiology. Pou1f1 loss-of-function heterozygotes are unaffected; Six3 heterozygotes have pituitary gland dysmorphology and incompletely ossified palate; and the Six3+/-; Pou1f1+/dw double heterozygote mice have a pronounced phenotype, including pituitary growth through the palate. The interaction of Pou1f1 and Six3 in mice supports the possibility of digenic pituitary disease in children. Disruption of Six3 expression in the oral ectoderm completely ablated anterior pituitary development, and deletion of Six3 in the neural ectoderm blocked the development of the pituitary stalk and both anterior and posterior pituitary lobes. Six3 is required in both oral and neural ectodermal tissues for the activation of signaling pathways and transcription factors necessary for pituitary cell fate. These studies clarify the mechanism of SIX3 action in pituitary development and provide support for a digenic basis for hypopituitarism.
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