ArticleThe Journal of clinical investigation2023
The long-range interaction between two GNAS imprinting control regions delineates pseudohypoparathyroidism type 1B pathogenesis.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 19 citations in OpenAlex.
- Population-scale detection of methylation outliers from long-read genome sequencing.medRxiv : the preprint server for health sciences · 2026Article
- The association of GNAS defects with pro-inflammatory adipokine levels in pseudohypoparathyroidism type 1.Journal of endocrinological investigation · 2026Article
- Pseudohypoparathyroidism in a Chinese girl: A case report.The Journal of international medical research · 2026Article
- A maternal exon H splice-site variant leading to pseudohypoparathyroidism type 1B with broad methylation defects in GNAS-differentially methylated regions.Clinical epigenetics · 2026Article
- Endocrine Disorders of Calcium Signaling in Children: Neuroendocrine Crosstalk and Clinical Implications.Cells · 2026Review
- Variability of endocrine findings with age and clinical severity in the long-term follow-up of pseudohypoparathyroidism: evidence of TRH resistance with central hypothyroidism.Frontiers in endocrinology · 2026Article
- Integrative analysis identifies STX16 as a prognostic and immune-associated biomarker in ccRCC.Scientific reports · 2025Article
- Congenital Imprinting Diseases: Aetiology, Pre- and Perinatal Manifestations, Diagnosis and Care of Affected Families and Pregnancies.Geburtshilfe und Frauenheilkunde · 2025Article
- Imprinting and skeletal disorders: lessons from pseudohypoparathyroidism and related disorders.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Review
- Defective GNAS imprinting due to splice site variants in pseudohypoparathyroidism type 1B.JCI insight · 2025Article
- Bidirectional disruption ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- A biallelically active embryonic enhancer dictates GNAS imprinting through allele-specific conformations.Nature communications · 2025Article
- Pseudohypoparathyroidism Presenting With Recurrent Twitching: Challenges Making a Diagnosis in a Low-Resource Environment.Case reports in endocrinology · 2025Article
- Recurrent small variants in NESP55/NESPAS associated with broad GNAS methylation defects and pseudohypoparathyroidism type 1B.JCI insight · 2024Article
- GNAS AS2 methylation status enables mechanism-based categorization of pseudohypoparathyroidism type 1B.JCI insight · 2024Article
- Review
- Pseudohypoparathyroidism: complex disease variants with unfortunate names.Journal of molecular endocrinology · 2024Review
- Pseudohypoparathyroidism Type IB with Subclinical Hypothyroidism: a Pedigree Investigation and Literature Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Article
- Editorial: Parathyroid disorders: updates of PTH/serum Ca2+ regulation and therapeutic prospects.Frontiers in endocrinology · 2023Article
- Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 3 countries.
Funding
Abstract
Genetic defects of GNAS, the imprinted gene encoding the stimulatory G protein α-subunit, are responsible for multiple diseases. Abnormal GNAS imprinting causes pseudohypoparathyroidism type 1B (PHP1B), a prototype of mammalian end-organ hormone resistance. Hypomethylation at the maternally methylated GNAS A/B region is the only shared defect in patients with PHP1B. In autosomal dominant (AD) PHP1B kindreds, A/B hypomethylation is associated with maternal microdeletions at either the GNAS NESP55 differentially methylated region or the STX16 gene located approximately 170 kb upstream. Functional evidence is meager regarding the causality of these microdeletions. Moreover, the mechanisms linking A/B methylation and the putative imprinting control regions (ICRs) NESP-ICR and STX16-ICR remain unknown. Here, we generated a human embryonic stem cell model of AD-PHP1B by introducing ICR deletions using CRISPR/Cas9. With this model, we showed that the NESP-ICR is required for methylation and transcriptional silencing of A/B on the maternal allele. We also found that the SXT16-ICR is a long-range enhancer of NESP55 transcription, which originates from the maternal NESP-ICR. Furthermore, we demonstrated that the STX16-ICR is an embryonic stage-specific enhancer enabled by the direct binding of pluripotency factors. Our findings uncover an essential GNAS imprinting control mechanism and advance the molecular understanding of PHP1B pathogenesis.
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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.