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This genetic disease is associated with changes in the <jats:italic>TNFRSF11B<\/jats:italic> gene encoding osteoprotegerin, an important regulator of osteoresorption. Most published JPD cases have been found to carry homozygous <jats:italic>TNFRSF11B<\/jats:italic> variants, while compound heterozygous variants in this gene have been reported only twice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and results<\/jats:title>\n            <jats:p>We report the first case of JPD diagnosed in the Czech Republic, who presented with a mild phenotype of this disease. The first bone fractures, appeared at 3\u00a0years of age. Other clinical manifestations included typical skeletal deformities, macrocephaly, arched chest, lower extremity valgosity, lateral bowing of the thighs, and anterior bowing of the shins. Minor mixed hearing impairment, angioid stripes of the choroidea, and temporary immunodeficiency were present among extra-skeletal findings. Sanger sequencing was performed on both the patient and the parents to test for the presence of <jats:italic>TNFRSF11B<\/jats:italic> sequence variants. Molecular genetic analysis showed unique compound heterozygous sequence variants in <jats:italic>TNFRSF11B<\/jats:italic>: a paternally inherited variant c.30\u2009+\u20095G\u2009&gt;\u2009A, p.(?) and a maternally inherited variant c.329G\u2009&gt;\u2009T, p.(Gly110Val). Both of the variants were analyzed by several in silico predictive tools indicating, for their strongly supported pathogenicity according to <jats:italic>American College of Medical Genetics and Genomics<\/jats:italic> standards. Furthermore, we present diagnostic findings, their treatment, and follow-up care.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The newly described variants of <jats:italic>TNFRSF11B<\/jats:italic> extend knowledge of this very rare disease. Early diagnosis and antiresorption treatment prevent further fractures and deformity progression, and improve the patient\u2019s quality of life. This example of osteoprotegerin deficiency may help us better understand its role in skeletal and non-skeletal systems.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13023-025-03804-2","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T12:30:09Z","timestamp":1754569809000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Juvenile Paget disease with unique compound heterozygous sequence variants in the TNFRSF11B gene"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7690-9745","authenticated-orcid":false,"given":"Jana","family":"Horackova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Taslerova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Bayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Nekvindova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ladislava","family":"Pavlikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M.","family":"Horacek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Palicka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"3804_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.metabol.2017.10.007","volume":"80","author":"SA Polyzos","year":"2018","unstructured":"Polyzos SA, Cundy T, Mantzoros CS. 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