{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:20:46Z","timestamp":1785853246410,"version":"3.56.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the clinical features of sporadic Paget\u2019s disease of bone (PDB) in China and further explore the underlying genetic abnormalities of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical characteristics, biochemical indices, bone turnover markers and radiographic examinations of the patients were collected. Genomic DNA was extracted from peripheral blood and whole-exome sequencing was carried out to identify the potential pathogenic genes. The pathogenicity of the variants was thereafter investigated by bioinformatics analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 50 patients (57.20 \u00b1 15.52 years, male\/female: 1.63: 1) with PDB were included and the mean onset age was 48.34 years (48.34 \u00b1 17.24 years). 94.0% of the patients exhibited symptomatic patterns described as bone pain (86.0%), elevated skin temperature at the lesion site (26.0%), bone deformity (22.0%) and local swelling (18.0%). The most frequently involved lesion sites were pelvis (52.0%), femur (42.0%), tibia (28.0%), skull (28.0%) and spine (18.0%), respectively. Additionally, 40.0% of them accompanied with osteoarthritis, 14.0% with pathological fractures, and the misdiagnosis rate of PDB was as high as 36.0%. Serum level of alkaline phosphatase was significantly increased, with the mean value of 284.00 U\/L (quartiles, 177.00-595.00 U\/L). Two heterozygous missense mutations of <jats:italic>SQSTM1<\/jats:italic> gene (c.1211T&amp;gt;C, M404T) and one novel heterozygous missense mutation in <jats:italic>HNRNPA2B1<\/jats:italic> gene (c.989C&amp;gt;T, p. P330L) were identified in our study. Moreover, several potential disease-causing genes were detected and markedly enriched in the pathways of neurodegeneration (including <jats:italic>WNT16<\/jats:italic>, <jats:italic>RYR3<\/jats:italic> and <jats:italic>RYR1<\/jats:italic> genes) and amyotrophic lateral sclerosis (ALS, including <jats:italic>NUP205<\/jats:italic>, <jats:italic>CAPN2<\/jats:italic>, and <jats:italic>NUP214<\/jats:italic> genes).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In contrast to Western patients, Chinese patients have an earlier onset age, more severe symptoms, and lower frequency of <jats:italic>SQSTM1<\/jats:italic> gene mutation (4.0%). Moreover, a novel heterozygous missense mutation in <jats:italic>HNRNPA2B1<\/jats:italic> gene was identified in one male patient with isolated bone phenotype. As for other genetic factors, it was indicated that <jats:italic>WNT16<\/jats:italic>, <jats:italic>RYR3<\/jats:italic>, <jats:italic>RYR1<\/jats:italic>, <jats:italic>NUP205<\/jats:italic>, <jats:italic>CAPN2<\/jats:italic> and <jats:italic>NUP214<\/jats:italic> genes may be potential pathogenic genes, pathways of neurodegeneration and ALS may play a vital role in the pathogenesis of PDB.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.850462","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T12:01:49Z","timestamp":1646827309000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Clinical Characteristics and Pathogenic Gene Identification in Chinese Patients With Paget\u2019s Disease of 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