{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T14:48:32Z","timestamp":1766760512420,"version":"3.41.2"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018812","name":"Instituto de Investigaci\u00f3n Marqu\u00e9s de Valdecilla","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018812","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Bone tissue homeostasis relies on the coordinated activity of the bone\u2010forming osteoblasts and bone\u2010resorbing osteoclasts. Osteomesopyknosis is considered a distinctive rare sclerosing skeletal disorder of unelucidated pathophysiology and presumably autosomal dominant transmission. However, the causal genes are unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We present a case report encompassing clinical assessments, imaging studies, and whole\u2010exome sequencing analysis, complemented by functional in\u00a0vitro experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This new case of osteomesopyknosis was associated with a missense <jats:italic>ALOX5<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data indicate impaired bone resorption as the underlying mechanism of this rare osteosclerosis, implicating <jats:italic>ALOX5<\/jats:italic> pathogenic variants as potential etiological factors.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2471","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T06:39:23Z","timestamp":1716878363000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Osteomesopyknosis associated with a novel <i>ALOX5<\/i> variant that impacts the RANKL pathway"],"prefix":"10.1002","volume":"12","author":[{"given":"Jose L.","family":"Fernandez\u2010Luna","sequence":"first","affiliation":[{"name":"Unidad de 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