Wang Chun, Zhang Bao-Hong, Zhang Hao, He Jin-Wei, Hu Yun-Qiu, Li Miao, Yue Hua, Hu Wei-Wei, Gu Jie-Mei, Liu Yu-Juan, Fu Wen-Zhen, Zhang Zhen-Lin
Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital affiliated with Shanghai Jiao Tong University, China.
Intern Med. 2013;52(2):187-92. doi: 10.2169/internalmedicine.52.8164. Epub 2013 Jan 15.
Osteosclerosis (OMIM: 144750) is a type of autosomal dominant bone disease caused by a mutation in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. The case of a Chinese family with two affected individuals is reported in the present study in order to investigate the clinical characteristics and virulence genes of this sclerosing bone disorder.
Biochemical and radiographic examinations and bone mineral density (BMD) and genetic analyses were performed in two patients and eight other family members.
The 40-year-old proband (II-1) and her 64-year-old mother (I-2) both had chronic lumbodorsal pain, an elongated mandible and torus palatinus in the center of the hard palate. No fractures were observed in any of the family members. Skull, mandibular and pelvic X-rays in each of the two patients revealed thickened cranial plates, an enlarged sella turcica, an elongated mandible and cortical thickening of the long bones. The BMD values of the two patients was significantly higher than the standard age- and sex-matched adult mean reference values. Both patients had higher serum sclerostin levels, while their renal function markers and serum calcium, phosphonium, parathyroid hormone (PTH) and 25(OH)D levels were within the normal ranges. The heterozygous missense mutation p.Ala242Thr in exon 4 of the LRP5 gene was detected in the two patients, while the other family members and 200 healthy donors had normal wild-type genotypes.
The A242T mutation in the LRP5 gene resulted in a high bone mass phenotype with an elongated mandible and torus palatinus in this osteosclerotic family.
骨硬化症（OMIM：144750）是一种常染色体显性遗传性骨病，由低密度脂蛋白受体相关蛋白5（LRP5）基因突变引起。本研究报告了一个有两名患者的中国家庭的病例，以调查这种硬化性骨病的临床特征和致病基因。
对两名患者和其他八名家庭成员进行了生化和影像学检查、骨密度（BMD）及基因分析。
40岁的先证者（II-1）及其64岁的母亲（I-2）均有慢性腰背痛、下颌骨延长和硬腭中部的腭隆突。所有家庭成员均未观察到骨折。两名患者的颅骨、下颌骨和骨盆X线检查均显示颅板增厚、蝶鞍扩大、下颌骨延长和长骨皮质增厚。两名患者的骨密度值均显著高于年龄和性别匹配的成年人标准平均参考值。两名患者的血清硬化蛋白水平均较高，而其肾功能指标及血清钙、磷、甲状旁腺激素（PTH）和25（OH）D水平均在正常范围内。在两名患者中检测到LRP5基因第4外显子的杂合错义突变p.Ala242Thr，而其他家庭成员和200名健康供者具有正常的野生型基因型。
LRP5基因中的A242T突变导致了这个骨硬化症家族出现高骨量表型，伴有下颌骨延长和腭隆突。
