Paget’s disease of bone (PDB) is characterized by focal or multifocal increase in bone turnover. One of the most well-established candidate genes for susceptibility to PDB is Sequestosome 1 (SQSTM1). Mutations in SQSTM1 have been documented among Western-European, British and American patients with PDB. However, there is no information on SQSTM1 mutation status in PDB patients from the Central- and Eastern-European regions. In this study, we conducted a mutation screening for SQSTM1 gene variants in 82 PDB patients and 100 control participants in Hungary. Mutations of SQSTM1 were detected in 18 PDB patients (21.95%); associations between genotype and clinical characteristics were also analyzed. Altogether, six different exonic alterations, including two types of UTR variants in the SQSTM1 gene, were observed in our PDB patients. Similarly, to previous genetic studies on Paget’s disease, our most commonly detected variant was the c.1175C > T (p.Pro392Leu) in nine cases (four in monostotic and five in polyostotic form). We have surveyed the germline SQSTM1 variant distribution among Hungarian patients with PDB. We also highlighted that the pattern of the analyzed disease-associated pathophysiological parameters could partially discriminate PDB patients with normal or mutant SQSTM1 genotype. However, our findings also underline and strengthen that not solely SQSTM1 stands in the background of the complex PDB etiology.

佩吉特骨病 (PDB) 的特征是骨转换的局灶性或多灶性增加。最成熟的 PDB 易感性候选基因之一是 Sequestosome 1 ( SQSTM1 )。在西欧、英国和美国的 PDB 患者中记录了SQSTM1的突变。然而，没有关于中欧和东欧地区 PDB 患者SQSTM1突变状态的信息。在这项研究中，我们对匈牙利的 82 名 PDB 患者和 100 名对照参与者进行了SQSTM1基因变异的突变筛查。SQSTM1的突变在 18 名 PDB 患者中检测到（21.95%）；还分析了基因型和临床特征之间的关联。在我们的 PDB 患者中总共观察到六种不同的外显子改变，包括SQSTM1基因中的两种 UTR 变体。类似地，对于之前关于佩吉特病的基因研究，我们最常检测到的变异是 9 例病例中的 c.1175C > T (p.Pro392Leu)（4 例为单骨型，5 例为多骨型）。我们调查了匈牙利 PDB 患者的种系SQSTM1变异分布。我们还强调，分析的疾病相关病理生理参数的模式可以部分区分具有正常或突变SQSTM1的 PDB 患者基因型。然而，我们的研究结果也强调并强化了SQSTM1 不仅处于复杂 PDB 病因学的背景中。