{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["13"],"submitter":["Tao X"],"funding":["National Natural Science Foundation of China"],"pubmed_abstract":["<h4>Objective</h4>To evaluate the clinical features of sporadic Paget's disease of bone (PDB) in China and further explore the underlying genetic abnormalities of the disease.<h4>Methods</h4>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.<h4>Results</h4>A total of 50 patients (57.20 ± 15.52 years, male/female: 1.63: 1) with PDB were included and the mean onset age was 48.34 years (48.34 ± 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 <i>SQSTM1</i> gene (c.1211T>C, M404T) and one novel heterozygous missense mutation in <i>HNRNPA2B1</i> gene (c.989C>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 <i>WNT16</i>, <i>RYR3</i> and <i>RYR1</i> genes) and amyotrophic lateral sclerosis (ALS, including <i>NUP205</i>, <i>CAPN2</i>, and <i>NUP214</i> genes).<h4>Conclusion</h4>In contrast to Western patients, Chinese patients have an earlier onset age, more severe symptoms, and lower frequency of <i>SQSTM1</i> gene mutation (4.0%). Moreover, a novel heterozygous missense mutation in <i>HNRNPA2B1</i> gene was identified in one male patient with isolated bone phenotype. As for other genetic factors, it was indicated that <i>WNT16</i>, <i>RYR3</i>, <i>RYR1</i>, <i>NUP205</i>, <i>CAPN2</i> and <i>NUP214</i> genes may be potential pathogenic genes, pathways of neurodegeneration and ALS may play a vital role in the pathogenesis of PDB."],"journal":["Frontiers in endocrinology"],"pagination":["850462"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8959906"],"repository":["biostudies-literature"],"pubmed_title":["Clinical Characteristics and Pathogenic Gene Identification in Chinese Patients With Paget's Disease of Bone."],"pmcid":["PMC8959906"],"pubmed_authors":["Yang X","Zhang G","Liu L","Chen Z","Zhang Z","Tao X","Wei Z","Yue H"],"additional_accession":[]},"is_claimable":false,"name":"Clinical Characteristics and Pathogenic Gene Identification in Chinese Patients With Paget's Disease of Bone.","description":"<h4>Objective</h4>To evaluate the clinical features of sporadic Paget's disease of bone (PDB) in China and further explore the underlying genetic abnormalities of the disease.<h4>Methods</h4>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.<h4>Results</h4>A total of 50 patients (57.20 ± 15.52 years, male/female: 1.63: 1) with PDB were included and the mean onset age was 48.34 years (48.34 ± 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 <i>SQSTM1</i> gene (c.1211T>C, M404T) and one novel heterozygous missense mutation in <i>HNRNPA2B1</i> gene (c.989C>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 <i>WNT16</i>, <i>RYR3</i> and <i>RYR1</i> genes) and amyotrophic lateral sclerosis (ALS, including <i>NUP205</i>, <i>CAPN2</i>, and <i>NUP214</i> genes).<h4>Conclusion</h4>In contrast to Western patients, Chinese patients have an earlier onset age, more severe symptoms, and lower frequency of <i>SQSTM1</i> gene mutation (4.0%). Moreover, a novel heterozygous missense mutation in <i>HNRNPA2B1</i> gene was identified in one male patient with isolated bone phenotype. As for other genetic factors, it was indicated that <i>WNT16</i>, <i>RYR3</i>, <i>RYR1</i>, <i>NUP205</i>, <i>CAPN2</i> and <i>NUP214</i> genes may be potential pathogenic genes, pathways of neurodegeneration and ALS may play a vital role in the pathogenesis of PDB.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022","modification":"2025-08-13T03:04:33.111Z","creation":"2025-04-04T21:34:01.635Z"},"accession":"S-EPMC8959906","cross_references":{"pubmed":["35355568"],"doi":["10.3389/fendo.2022.850462"]}}