Novel NPR2 heterozygous variant in a familial short stature and the therapeutic response to rhGH: a case report.

Authors

Dongmei Wang, Xuyun Hu, Shan Su, Yajun Yi, Yaxing Zeng, Ke Zhang, Yuan Ding, Chanjuan Hao, Rui Wang, Di Wu

Published in

Journal of pediatric endocrinology & metabolism : JPEM. Jul 14, 2026. Epub Jul 14, 2026.

Abstract

Natriuretic peptide receptor 2 (NPR2) expression in the hypertrophic zone of the growth plate is essential for endochondral ossification. Heterozygous variants in the NPR2 gene have been identified in 2-6 % of idiopathic short stature cases. Here, we present a large family with a novel heterozygous NPR2 variant, detailing endocrine features and long-term recombinant human growth hormone (rhGH) therapy outcomes.
A total of 18 subjects among the family exhibited short stature. The proband was a 5.2-year-old boy presenting with proportionate short stature, delayed bone age, facial abnormalities, premature delivery, small for gestational age and hypospadias. Whole-exome sequencing revealed a novel heterozygous variant, c.553G>A variant, in the NPR2 gene, leading to the missense variant site in the extracellular ligand-binding domain of NPR2 protein. All the family members with NPR2 gene mutation demonstrated marked short stature, except for four subjects. Five other children who received rhGH therapy were also included in the results. The difference between bone age and chronological age in all six children ranged from -2.3 to 0 years. The average height SDS before rhGH treatment ranged from -4.01 to -1.20 (-2.59 ± 1.16). The treatment has lasted for 4.68 ± 2.68 years, and height SDS improved by 1.54 ± 0.78 after rhGH therapy.
Our study confirms NPR2 variants as a cause of familial short stature (FSS), with variability in phenotypes, clinical features, and rhGH response, even within families. Early genetic testing might be crucial for offspring with FSS, as it allows for timely initiation of rhGH therapy.

PMID:
42438924
Bibliographic data and abstract were imported from PubMed on 13 Jul 2026.

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