ArticleJCI insight2020
Loss of MAGEL2 in Prader-Willi syndrome leads to decreased secretory granule and neuropeptide production.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 68 citations in OpenAlex.
- CRISPR screening identifies TRIM27 as a destabilizer of the Smith-Magenis syndrome protein RAI1.Genetics · 2026Article
- Multi-omics profiling reveals MAGEL2-driven defects in human corticogenesis shared across Prader-Willi and Schaaf-Yang syndromes.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms of USP7/MAGEL2 Complex Assembly and Its Mutational Disruption in Neurodevelopmental Diseases.bioRxiv : the preprint server for biology · 2026Article
- Divergent epigenetic profile underlie pubertal disorders in MKRN3-associated central precocious puberty and Prader-Willi syndrome: insights from a frameshift variant.World journal of pediatrics : WJP · 2026Article
- Clinical Presentation, Genetics, and Laboratory Testing with Integrated Genetic Analysis of Molecular Mechanisms in Prader-Willi and Angelman Syndromes: A Review.International journal of molecular sciences · 2026Review
- Case Report: Schaaf-Yang Syndrome Milder Phenotype Due to Potential Pathogenic Novel Missense Variant as an Unusual Cause of Obesity in a Pediatric Patient.The application of clinical genetics · 2026Article
- Clinical and genetic basis of congenital gonadotropin deficiency.Human reproduction open · 2026Article
- Article
- Neuropeptides and the Autonomic Nervous System in Prader-Willi Syndrome.International journal of molecular sciences · 2025Review
- Neuroendocrinology and the Genetics of Obesity.Endocrinology · 2025Review
- Selective changes in vasopressin neurons and astrocytes in the suprachiasmatic nucleus of Prader-Willi syndrome subjects.Journal of neuroendocrinology · 2025Article
- Activation of the imprinted Prader-Willi syndrome locus by CRISPR-based epigenome editing.Cell genomics · 2025Article
- Article
- MAGEL2 (patho-)physiology and Schaaf-Yang syndrome.Developmental medicine and child neurology · 2025Review
- Sex differences in MAGEL2 gene promoter methylation in high functioning autism - trends from a pilot study using nanopore Cas9 targeted long read sequencing.BMC medical genomics · 2024Article
- Neuropeptide therapeutics to repress lateral septum neurons that disable sociability in an autism mouse model.Cell reports. Medicine · 2024Article
- Characterization of Circulating Protein Profiles in Individuals with Prader-Willi Syndrome and Individuals with Non-Syndromic Obesity.Journal of clinical medicine · 2024Article
- Truncated variants of MAGEL2 are involved in the etiologies of the Schaaf-Yang and Prader-Willi syndromes.American journal of human genetics · 2024Article
- Emerging Perspectives on Prime Editor Delivery to the Brain.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Disengagement of somatostatin neurons from lateral septum circuitry by oxytocin and vasopressin restores social-fear extinction and suppresses aggression outbursts in Prader-Willi syndrome model.Biological psychiatry · 2024Article
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 1 country.
Funding
Abstract
Prader-Willi syndrome (PWS) is a developmental disorder caused by loss of maternally imprinted genes on 15q11-q13, including melanoma antigen gene family member L2 (MAGEL2). The clinical phenotypes of PWS suggest impaired hypothalamic neuroendocrine function; however, the exact cellular defects are unknown. Here, we report deficits in secretory granule (SG) abundance and bioactive neuropeptide production upon loss of MAGEL2 in humans and mice. Unbiased proteomic analysis of Magel2pΔ/m+ mice revealed a reduction in components of SG in the hypothalamus that was confirmed in 2 PWS patient-derived neuronal cell models. Mechanistically, we show that proper endosomal trafficking by the MAGEL2-regulated WASH complex is required to prevent aberrant lysosomal degradation of SG proteins and reduction of mature SG abundance. Importantly, loss of MAGEL2 in mice, NGN2-induced neurons, and human patients led to reduced neuropeptide production. Thus, MAGEL2 plays an important role in hypothalamic neuroendocrine function, and cellular defects in this pathway may contribute to PWS disease etiology. Moreover, these findings suggest unanticipated approaches for therapeutic intervention.
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