Clinical evaluation and molecular analysis of genetic and epigenetic inactivation defects in GNAS in children: A multicenter experience in China
Authors' conclusion
Our findings suggest that molecular screening can be highly specific in patients with parathyroid hormone resistance. Furthermore, we found significant overlap in the clinical features between patients with iPPSD2 and iPPSD3, suggesting that a combination of molecular genetic diagnosis and clinical evaluation may be the better approach for fully understanding GNAS inactivation defects disorders.
Study context
- Population
- Children with clinically diagnosed PHP, PPHP or progressive osseous heteroplasia (POH), China70 genetically analysed
- Participants
- 87 children
- Comparison
- iPPSD2 vs iPPSD3
- iPPSD2n = 31
- iPPSD3n = 39
- Outcome
- Genetic and epigenetic GNAS defects
Methodological detailsclinical evaluation and molecular analysis, paediatric
- Clinical evaluation and molecular analysis
- Paediatric
Main finding
As reported in the abstract
Pathogenic GNAS variants (iPPSD2), mostly PHP1A, 2 cases each of PPHP and POH
31 patients
GNAS imprinting defects (iPPSD3): 11 PHP1A, 28 PHP1B
39 patients
Further findings
Presenting complaints
- Sluggish height growth and hypocalcemia-related symptoms common in PHP1A; hypocalcemia-related symptoms typical in PHP1B
Albright hereditary osteodystrophy (AHO) phenotypes of PHP1A across cohorts
- AHO phenotypes varied among the 4 cohorts
rhGH treatment in PHP1A
- PHP1A patients treated with rhGH showed improved height and growth rates
- 3 patients
Original publication
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