A novel frameshift deletion in PLS3 causing severe primary osteoporosis
A novel frameshift deletion in PLS3 causing severe primary osteoporosis
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DOI：
10.1038/s10038-018-0472-5
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发表时间：
2018-07-01
影响因子：
3.5
通讯作者：
Doulgeraki, Artemis
中科院分区：
文献类型：
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作者：
Costantini, Alice;Krallis, Panagiotis N.;Doulgeraki, Artemis
编码plastin-3（PLS 3）的基因突变最近被认为与严重的原发性骨质疏松症有关。plastin-3的分子功能尚未完全了解。由于PLS 3位于X染色体上，男性通常比女性受到更严重的影响。迄今为止，在大约20名低骨矿物质密度（BMD）的年轻患者中报告了PLS 3突变。我们描述一个8岁的希腊男孩，患有严重的原发性骨质疏松症，多个椎体压缩性骨折和一个低能量长骨骨折。他的临床表现与成骨不全一致，包括蓝色巩膜、关节过度活动、骨密度低、脊柱后凸、双侧传导性听力损失和轻度畸形特征。原发性骨质疏松症的家族史为阴性。通过桑格测序排除COL 1A 1和COL 1A 2突变。然而，PLS 3的桑格测序导致鉴定从头移码缺失，NM_005032：c.1096_1100delAACTT，p.（Asn 366 Serfs *5），在外显子10中证实了PLS 3骨质疏松症的诊断。总之，我们描述了一种新的移码缺失PLS 3导致严重的原发性骨质疏松症的男孩。我们的发现强调了I型胶原和PLS 3相关骨骼脆性之间的临床重叠，并强调了PLS 3筛查在多发性骨折患者中的重要性，以进行适当的遗传咨询。
Mutations in the gene encoding plastin-3, PLS3, have recently been associated to severe primary osteoporosis. The molecular function of plastin-3 is not fully understood. Since PLS3 is located on the X chromosome, males are usually more severely affected than females. PLS3 mutations have thus far been reported in approximately 20 young patients with low bone mineral density (BMD). We describe an 8-year-old Greek boy with severe primary osteoporosis with multiple vertebral compression fractures and one low-energy long bone fracture. His clinical manifestations were consistent with osteogenesis imperfecta, including blue sclerae, joint hypermobility, low bone mineral density, kyphosis, bilateral conductive hearing loss, and mild dysmorphic features. The family history was negative for primary osteoporosis. COL1A1 and COL1A2 mutations were excluded by Sanger sequencing. However, Sanger sequencing of PLS3 led to the identification of a de novo frameshift deletion, NM_005032: c.1096_1100delAACTT, p.(Asn366Serfs*5), in exon 10 confirming the diagnosis of PLS3 osteoporosis. In conclusion, we describe a novel frameshift deletion in PLS3 causing severe primary osteoporosis in a boy. Our finding highlights the clinical overlap between type I collagen and PLS3-related skeletal fragility and underscores the importance of PLS3 screening in patients with multiple fractures to enable proper genetic counseling.