Department of Pediatric Genetics, Cerrahpaşa Medical School, Istanbul University, Istanbul, Turkey.
Horm Res Paediatr. 2012;77(2):115-20. doi: 10.1159/000336193. Epub 2012 Mar 23.
BACKGROUND/AIMS: Osteoporosis-pseudoglioma (OPPG) syndrome is a rare disorder characterized by congenital or infancy-onset visual loss and severe juvenile osteoporosis. OPPG is caused by homozygous mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. We present three novel homozygous LRP5 mutations found in 3 unrelated Turkish children with consanguineous parents, along with clinical phenotypes and response to treatment with bisphosphonates (bisP).
METHODS/RESULTS: The LRP5 gene was analyzed by direct sequencing after PCR amplification. Mutation screening for LRP5 revealed homozygous nonsense R1002X mutation in the first patient and homozygous missense mutations V336M and G507S in the second and third patient, respectively. The parents were heterozygous for these mutations. The patients' eye symptoms began during the first months of life but the OPPG diagnoses were made based on skeletal deformities and osteopenia after 4 years of age. The patients' bone mineral density Z scores were very low and consistent with osteopenia. All patients were treated with bisP for 3.5-7 years.
We report three novel LRP5 mutations in 3 Turkish patients with OPPG. We show that the response of bisP therapy has improved the lumbar spinal bone mineral density Z scores and the patients' quality of life as the bone pains decreased.
背景/目的：骨质疏松-假瘤（OPPG）综合征是一种罕见疾病，其特征为先天性或婴儿期发病的视力丧失和严重的青少年骨质疏松症。OPPG 是由载脂蛋白脂蛋白受体相关蛋白 5（LRP5）基因的纯合突变引起的。我们报告了 3 名土耳其近亲父母的孩子中发现的 3 种新的 LRP5 纯合突变，以及临床表型和双膦酸盐（bisP）治疗的反应。
方法/结果：通过 PCR 扩增后直接测序分析 LRP5 基因。LRP5 的突变筛查显示，第一个患者存在纯合无义 R1002X 突变，第二个和第三个患者分别存在纯合错义 V336M 和 G507S 突变。父母均为这些突变的杂合子。患者的眼部症状在生命的头几个月开始，但在 4 岁后根据骨骼畸形和骨质疏松症诊断为 OPPG。患者的骨矿物质密度 Z 分数非常低，与骨质疏松症一致。所有患者均接受 bisP 治疗 3.5-7 年。
我们报告了 3 名土耳其 OPPG 患者的 3 种新的 LRP5 突变。我们表明，bisP 治疗的反应改善了腰椎骨矿物质密度 Z 评分和患者的生活质量，因为骨痛减轻了。
