Identification of pathogenic ACAN variants in healthy children with normal height and advanced bone age

María Isabel Hernández^{1

2}, Vivian Gallardo^{3

4}, Nancy Unanue^{5

6}, Hermine van Duyvenvoorde⁷, María Verónica Mericq¹

Affiliations

¹ Faculty of Medicine, Institute of Maternal and Child Research (IDIMI), University of Chile, Santiago, Chile.
² Institute of Neurosurgery Dr. Alfonso Asenjo, Santiago, Chile.
³ Hospital Exequiel González Cortes, Santiago, Chile.
⁴ Department of Pediatrics, Clínica Universidad de los Andes, Santiago, Chile.
⁵ Hospital San Borja Arriarán, Santiago, Chile.
⁶ Department of Pediatrics, Clínica Las Condes, Santiago, Chile.
⁷ Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.

María Isabel Hernández et al. J Pediatr Endocrinol Metab. 2025.

. 2025 Aug 28.

doi: 10.1515/jpem-2025-0408. Online ahead of print.

María Isabel Hernández^{1

2}, Vivian Gallardo^{3

4}, Nancy Unanue^{5

6}, Hermine van Duyvenvoorde⁷, María Verónica Mericq¹

¹ Faculty of Medicine, Institute of Maternal and Child Research (IDIMI), University of Chile, Santiago, Chile.
² Institute of Neurosurgery Dr. Alfonso Asenjo, Santiago, Chile.
³ Hospital Exequiel González Cortes, Santiago, Chile.
⁴ Department of Pediatrics, Clínica Universidad de los Andes, Santiago, Chile.
⁵ Hospital San Borja Arriarán, Santiago, Chile.
⁶ Department of Pediatrics, Clínica Las Condes, Santiago, Chile.
⁷ Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.

No abstract available

Keywords: ACAN; advanced bone age; growth plate; height.

References

1. Kiani, C, Chen, L, Wu, YJ, Yee, AJ, Yang, BB. Structure and function of aggrecan. Cell Res. 2002;12:19–32. https://doi.org/10.1038/sj.cr.7290106 . - DOI
1. Domowicz, MS, Cortes, M, Henry, JG, Schwartz, NB. Aggrecan modulation of growth plate morphogenesis. Dev Biol 2009;329:242–57. https://doi.org/10.1016/j.ydbio.2009.02.024 . - DOI
1. Lin, L, Li, M, Luo, J, Li, P, Zhou, S, Yang, Y, et al.. A high proportion of novel ACAN mutations and their prevalence in a large cohort of Chinese short stature children. J Clin Endocrinol Metab 2021;106:e2711–19. https://doi.org/10.1210/clinem/dgab088 . - DOI
1. Hauer, NN, Sticht, H, Boppudi, S, Büttner, C, Kraus, C, Trautmann, U, et al.. Genetic screening confirms heterozygous mutations in ACAN as a major cause of idiopathic short stature. Sci Rep 2017;7:12225. https://doi.org/10.1038/s41598-017-12465-6 . - DOI
1. Wu, S, Wang, C, Cao, Q, Zhu, Z, Liu, Q, Gu, X, et al.. The spectrum of ACAN gene mutations in a selected Chinese cohort of short stature: genotype-phenotype correlation. Front Genet 2022;13:891040. https://doi.org/10.3389/fgene.2022.891040 . - DOI