Department of Orthopaedic Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
Bone. 2010 Sep;47(3):701-5. doi: 10.1016/j.bone.2010.06.005. Epub 2010 Jun 18.
Rett syndrome (RTT) is a common X-linked neurodevelopmental disorder caused by mutations in the coding region of methyl-CpG-binding 2 (MECP2) gene. Patients with RTT have a low bone mineral density and increased risk of fracture. However, very little is known if bone matrix mineralization is altered in RTT. A 17-year-old girl with a classical form of RTT with a heterozygous nonsense mutation in exon 3 in the MECP2-gene was treated in our hospital. Her femoral neck BMD is 43.3% below the 3rd percentile when compared to age and sex-matched controls. She underwent surgery for correction of her scoliosis, which provided a unique opportunity to obtain bone tissue to study bone matrix mineralization (Bone Mineralization Density Distribution-BMDD) using quantitative backscattered electron imaging (qBEI) and histomorphometry. BMDD outcomes were compared to recently published normative reference data for young individuals. qBEI analysis showed a significant shift to lower matrix mineralization despite histomorphometric indices indicate a low bone turnover. There was a reduction in CaMean (-7.92%) and CaPeak (-3.97%), which describe the degree of mineralization. Furthermore the fraction of low mineralized matrix (CaLow: +261.84%) was dramatically increased, which was accompanied with an increase in the heterogeneity of mineralization (CaWidth: +86.34%). Our findings show a significantly altered bone matrix mineralization of a typical patient with RTT. This may partly explain the low bone density seen in these patients. These results also warrant further studies on the molecular role of MECP2 in bone matrix mineralization.
雷特综合征（RTT）是一种常见的 X 连锁神经发育障碍，由编码区甲基化CpG 结合蛋白 2（MECP2）基因突变引起。患有 RTT 的患者骨密度低，骨折风险增加。然而，对于 RTT 中骨基质矿化是否改变知之甚少。我们医院收治了一名 17 岁的女孩，她患有经典型 RTT，MECP2 基因外显子 3 存在杂合无义突变。与年龄和性别匹配的对照组相比，她的股骨颈 BMD 低 3 个百分位数的 43.3%。她因脊柱侧凸接受了手术矫正，这为获得骨组织提供了一个独特的机会，以便使用定量背散射电子成像（qBEI）和组织形态计量学研究骨基质矿化（骨矿化密度分布-BMDD）。将 BMDD 结果与最近公布的年轻个体的正常参考数据进行了比较。qBEI 分析显示，尽管组织形态计量学指标表明骨转换率低，但基质矿化程度明显向较低方向移动。CaMean（-7.92%）和 CaPeak（-3.97%）降低，这两个指标描述了矿化程度。此外，低矿化基质的分数（CaLow：+261.84%）显著增加，同时矿化的异质性增加（CaWidth：+86.34%）。我们的研究结果表明，典型的 RTT 患者的骨基质矿化明显改变。这可能部分解释了这些患者骨密度低的原因。这些结果还需要进一步研究 MECP2 在骨基质矿化中的分子作用。
