Osteoporosis Caused by Mutations in PLS3: Clinical and Bone Tissue Characteristics
Osteoporosis Caused by Mutations in PLS3: Clinical and Bone Tissue Characteristics
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DOI：
10.1002/jbmr.2208
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发表时间：
2014-08-01
影响因子：
6.2
通讯作者：
Rauch, Frank
中科院分区：
文献类型：
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作者：
Fahiminiya, Somayyeh;Majewski, Jacek;Rauch, Frank
PLS 3突变已被确定为儿童骨脆性的原因，但与PLS 3突变相关的骨表型尚未详细报道。PLS 3位于X染色体上，编码肌动蛋白结合蛋白质plastin 3。在这里，我们描述了来自2个家族的4名男孩的骨骼发现，这些男孩具有PLS 3突变（家族1中c.994_995delGA; p.Asp332*;家族2中c.1433T>C; p.Leu478Pro）。当在4至8岁之间进行首次评估时，这些男孩有1至4次长骨骨折的病史。在每个男孩中发现了轻度椎体压缩性骨折。无明显的皮肤外疾病表现。腰椎区域骨密度（LS-aBMD）Z评分范围为-1.7至-3.5，但身高正常。2例患者髂骨骨组织形态计量学显示骨小梁体积和类骨质成熟时间较低，但骨形成率和破骨细胞表面正常。定量背散射电子成像（qBEI）未显示骨矿化密度分布的重大异常。来自家庭1的2名男孩口服阿仑膦酸钠6年，使LS-aBMD正常化。4名男孩的母亲没有骨折史，LS-aBMD正常。然而，其中一位母亲的桡骨远端骨量较低，通过外周定量计算机断层扫描（pQCT）测量。总之，PLS 3的半合子突变与儿童骨质疏松症和骨脆性相关，但与I型胶原编码基因突变引起的骨脆性相反，矿化骨基质没有过度矿化。(C)2014年美国骨与矿物质研究学会。
Mutations in PLS3 have been identified as a cause of bone fragility in children, but the bone phenotype associated with PLS3 mutations has not been reported in detail. PLS3 is located on the X chromosome and encodes the actin-binding protein plastin 3. Here we describe skeletal findings in 4 boys from 2 families with mutations in PLS3 (c.994_995delGA; p.Asp332* in family 1; c.1433T>C; p. Leu478Pro in family 2). When first evaluated between 4 and 8 years of age, these boys had a history of one to four long-bone fractures. Mild vertebral compression fractures were identified in each boy. No obvious extraskeletal disease manifestations were present. Lumbar spine areal bone mineral density (LS-aBMD) Z-scores ranged from -1.7 to -3.5, but height was normal. Iliac bone histomorphometry in 2 patients showed low trabecular bone volume and a low osteoid maturation time but normal bone formation rate and osteoclast surface. Quantitative backscattered electron imaging (qBEI) did not reveal a major abnormality in bone mineralization density distribution. The 2 boys from family 1 received oral alendronate for 6 years, which normalized LS-aBMD. The mothers of the 4 boys did not have a history of fractures and had normal LS-aBMD. However, one of these mothers had low bone mass at the distal radius, as measured by peripheral quantitative computed tomography (pQCT). In conclusion, hemizygous mutations in PLS3 are associated with osteoporosis and bone fragility in childhood, but in contrast to bone fragility caused by mutations in collagen type I encoding genes, there is no hypermineralization of mineralized bone matrix. (C) 2014 American Society for Bone and Mineral Research.