Shriners Hospital for Children - Canada, McGill University, Montreal, QC, Canada; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, ON, Canada.
Shriners Hospital for Children - Canada, McGill University, Montreal, QC, Canada.
Bone. 2020 May;134:115261. doi: 10.1016/j.bone.2020.115261. Epub 2020 Feb 3.
Heterozygous mutations in the gene encoding the sphingomyelin synthase 2, SGMS2, have recently been linked to childhood-onset osteoporosis and skeletal dysplasia. One nonsense variant at position c.148C>T (p.Arg50*) has been associated with mild bone fragility with or without cranial sclerosis. Here we assessed the effect of the SGMS2 p.Arg50* variant in two unrelated probands with childhood-onset osteoporosis and their unaffected family members. We found that the p.Arg50* variant was associated with phenotypic variability, ranging from absence of a bone phenotype to severe vertebral compression fractures and low lumbar spine areal bone mineral density (BMD) as measured by dual energy x-ray absorptiometry. Peripheral quantitative computed tomography of the radius and tibia in the two probands revealed low cortical volumetric BMD and reduced cortical thickness. In addition, both probands were obese and suffered from muscle function deficits compared to sex- and age-matched controls. Long-term bisphosphonate treatment was associated with reshaping of previously compressed vertebral bodies.
最近，编码鞘磷脂合酶 2（SGMS2）的基因中的杂合突变与儿童期骨质疏松症和骨骼发育不良有关。位置 c.148C>T（p.Arg50*）的一个无义变异与伴有或不伴有颅硬化的轻度骨脆弱性有关。在这里，我们评估了 SGMS2 p.Arg50变体在两名患有儿童期骨质疏松症的无关先证者及其未受影响的家族成员中的作用。我们发现，p.Arg50变体与表型变异性相关，从没有骨表型到严重的椎体压缩性骨折和低腰椎面积骨密度（BMD），通过双能 X 射线吸收法测量。两名先证者的桡骨和胫骨外周定量计算机断层扫描显示皮质体积 BMD 低，皮质厚度减少。此外，与性别和年龄匹配的对照组相比，两名先证者均肥胖，并患有肌肉功能缺陷。长期使用双膦酸盐治疗与先前受压的椎体重塑有关。
