Studies on mice have shown that the Smad Ubiquitin Regulatory Factor-1 (SMURF1) gene negatively regulates osteoblast function and the response to bone morphogenetic protein in a dose-dependent fashion (Chan et al. in Mol Cell Biol 27(16):5776-5789, https://doi.org/10.1128/MCB.00218-07, 2007; Yamashita et al. in Cell 121(1):101-113, https://doi.org/10.1016/j.cell.2005.01.035, 2005). In addition, a tumorigenic role for SMURF1 has been implicated due to the interference with apoptosis signals (Nie et al. in J Biol Chem 285(30):22818-22830, https://doi.org/10.1074/jbc.M110.126920, 2010; Wang et al. in Nat Commun 5:4901, https://doi.org/10.1038/ncomms5901, 2014). A 10-year-old girl with a history of severe developmental delay, infantile seizures, and B-cell lymphoma, in remission for approximately 3.5 years, was referred to the metabolic bone clinic for fractures and low bone mineral density. Array comparative genomic hybridization revealed a pathogenic microduplication in chromosome 7 at bands 7q21.3q22.1 that encompasses the SMURF1 gene. The clinical features of this child are congruous with the phenotype as ascribed excess Smurf1 mutations in mice. This is the first case description of osteoporosis in a child secondary to a microduplication involving SMURF1 gene.

中文翻译：

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SMURF1基因复制继发的脆弱骨骼。

对小鼠的研究表明，Smad泛素调节因子1（SMURF1）基因以剂量依赖性方式负面调节成骨细胞功能和对骨形态发生蛋白的反应（Chan等人在Mol Cell Biol 27（16）：5776- 5789，https://doi.org/10.1128/MCB.00218-07，2007; Yamashita等人在Cell 121（1）：101-113，https://doi.org/10.1016/j.cell.2005.01 .035，2005）。另外，由于干扰细胞凋亡信号，已经暗示了SMURF1的致瘤作用（Nie等人在J Biol Chem 285（30）：22818-22830，https：//doi.org/10.1074/jbc.M110。 126920，2010； Wang等人，Nat Commun 5：4901，https：//doi.org/10.1038/ncomms5901，2014）。一位10岁的女孩，有严重的发育迟缓，婴儿癫痫发作和B细胞淋巴瘤病史，可缓解约3.5年，因骨折和骨矿物质密度低而被转诊至新陈代谢骨诊所。阵列比较基因组杂交揭示了包含SMURF1基因的7q21.3q22.1条带在染色体7中的致病性微复制。这个孩子的临床特征与小鼠表型过量的Smurf1突变表型相吻合。这是继涉及SMURF1基因的微复制后继发于儿童骨质疏松症的首例病例。