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Updated: Jun 3, 2025
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In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
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Loss-of-Function GHSR Variants Are Associated With Short Stature and Low IGF-I
Lauren D Punt1, Sander Kooijman2,3, Noa J M Mutsters4
1Division of Pediatric Endocrinology, Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Centre, 2333 ZA Leiden, the Netherlands.
The Journal of Clinical Endocrinology and Metabolism
|January 9, 2025
Summary
Growth hormone secretagogue receptor (GHSR) haploinsufficiency in children causes short stature. These patients showed a significant height gain after growth hormone (GH) treatment, supporting GHSR's role in GH secretion.
Area of Science:
- Endocrinology
- Genetics
- Pediatrics
Background:
- The growth hormone (GH) secretagogue receptor (GHSR) is crucial for GH secretion from the pituitary gland.
- GHSR variants can lead to impaired GH secretion, but their clinical significance in short stature remains unclear.
Purpose of the Study:
- To investigate the phenotype of GHSR haploinsufficiency in children with short stature.
- To evaluate the growth response to GH treatment in these patients.
Main Methods:
- A case series of 26 patients with short stature and heterozygous GHSR variants.
- In vitro functional studies assessed receptor activity and protein levels.
- Clinical data included height, IGF-I levels, and response to GH therapy.
Main Results:
- Ten GHSR variants were identified, six novel, with partial or complete loss of function.
- Patients presented with proportionate short stature, failure to thrive, and low appetite.
- GH treatment resulted in significant height gain over two years.
Conclusions:
- GHSR haploinsufficiency is associated with short stature in children.
- These patients demonstrate a robust response to GH treatment.
- The findings reinforce the role of GHSR in regulating GH secretion.
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