ArticleThe Journal of clinical endocrinology and metabolism2025
Loss-of-Function GHSR Variants Are Associated With Short Stature and Low IGF-I.
Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.
What it found
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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.
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Who cites it
5 citing papers in PubMed.
- Reproductive experience promotes permanent body growth independently of growth hormone.bioRxiv : the preprint server for biology · 2026Article
- Unraveling the Genetic Heterogeneity of Isolated Growth Hormone Deficiency: Insights from the GENHYPOPIT Cohort.Hormone research in paediatrics · 2026Article
- Growth hormone treatment outcomes in children with genetic isolated growth hormone deficiency.European journal of pediatrics · 2025Article
- MRAP2 potentiates GPCR signaling by conserved mechanisms that are disrupted by obesity-associated genetic variants.bioRxiv : the preprint server for biology · 2025Article
- Diagnostic Challenges of Short Stature and Growth Hormone Insufficiency Across Different Genetic Etiologies.Biomedicines · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
29 authors.
Funding
Abstract
contextThe growth hormone (GH) secretagogue receptor, encoded by GHSR, is expressed on somatotrophs of the pituitary gland. Stimulation with its ligand ghrelin, as well as its constitutive activity, enhances GH secretion. Studies in knockout mice suggest that heterozygous loss-of-function of GHSR is associated with decreased GH response to fasting, but patient observations in small case reports have been equivocal.
objectiveThis work aims to establish the phenotype of GHSR haploinsufficiency and its growth response to GH treatment.
methodsThis case series includes 26 patients with short stature and heterozygous GHSR variants. Pathogenicity was studied in vitro using total protein levels, cell surface expression, and receptor activity in basal, stimulated, and inhibited states.
resultsTen different variants were identified, of which 6 were novel. Variants showed either partial or complete loss of function, primarily through loss of constitutive activity. Patients (aged 4.0-15.1 years) had proportionate short stature (height -2.8 ± 0.5 SDS), failure to thrive with low appetite (n = 4), a mean serum insulin-like growth factor-I (IGF-I) of -1.6 ± 0.7 SDS, and a normal stimulated GH response. Nine patients received GH treatment, showing a height gain of 0.9 ± 0.4 SDS after 1 year and 1.5 ± 0.4 SDS after 2 years (n = 5).
conclusionThis study combines phenotypical and functional data in a uniquely large group of children with short stature carrying GHSR variants, and shows their good response to GH treatment. The results strengthen the hypothesis of GHSR's role in GH secretion.
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