@article{10902/33812,
year = {2024},
url = {https://hdl.handle.net/10902/33812},
abstract = {Background: Bone tissue homeostasis relies on the coordinated activity of the bone-forming osteoblasts and bone-resorbing osteoclasts. Osteomesopyknosis is considered a distinctive rare sclerosing skeletal disorder of unelucidated pathophysiology and presumably autosomal dominant transmission. However, the causal genes are unknown.
Methods: We present a case report encompassing clinical assessments, imaging studies, and whole-exome sequencing analysis, complemented by functional in vitro experiments.
Results: This new case of osteomesopyknosis was associated with a missense ALOX5 variant predicted to induce protein misfolding and proteasomal degradation. Transfection experiments demonstrated that the variant was associated with reduced protein levels restored by proteasomal inhibition with bortezomib. Likewise, gene expression analysis showed that the mutated gene was associated with a decreased RANKL/OPG ratio, which is a critical driver of osteoclast precursor differentiation.
Conclusion: Our data indicate impaired bone resorption as the underlying mechanism of this rare osteosclerosis, implicating ALOX5 pathogenic variants as potential etiological factors.},
organization = {ACKNOWLEDGMENTS: This study was funded in part by Instituto de Investigación Marqués de Valdecilla (IDIVAL APG/03).},
publisher = {Wiley-Blackwell},
publisher = {Molecular Genetics and Genomic Medicine, 2024, 12, e2471},
title = {Osteomesopyknosis associated with a novel ALOX5 variant that impacts the RANKL pathway},
author = {Fernández Luna, José Luis and Hernández Hernández, José Luis and Curiel Del Olmo, Soraya and Martínez-Amador, Néstor A. and Vega, Ana I. and Quirce Pisano, María Remedios and Montes Moreno, Santiago and Gutiérrez, Olga and Real Bolt, Álvaro del and Sañudo Campo, María Carolina and Riancho Moral, José Antonio},
}