摘要
目的本研究对一个常染色体隐性遗传的骨质硬化症家系进行了研究,以确定本家系骨质硬化症的致病基因。方法采用双能X线吸收法(DXA)测定骨密度(BMD)。提取11个家系成员及180名正常对照者外周血DNA,用基因测序排除已知与骨质硬化症相关的11个基因的突变后,做全基因组扫描、精细基因定位及单倍型分析确定致病基因候选区。采用TRAP染色试剂盒行骨活检标本破骨细胞染色。结果该常染色体隐性骨质硬化症家系无已知与骨质硬化症相关的基因突变。全基因组扫描、精细基因定位及单倍型分析结果显示,染色体19q13.2～q13.3的D19S197～D19S545之间的8.36cm范围为致病基因候选区,连锁分析最大LOD值Zmax=2.907(θ=0时)。骨活检标本的TRAP染色结果显示,与性别和年龄匹配的正常人相比,骨质硬化患者髂嵴破骨细胞数量减少。结论该常染色体隐性骨质硬化症家系患者破骨细胞减少,19号染色体q13.2～q13.3有骨质硬化症易感基因存在,为尚未报道的常染色体隐性骨质硬化症特色类型。
Objective A Chinese family with autosomal recessive osteopetrosis was investigated with the aim of identifying novel gene mutations associated with osteopetrosis in this Chinese family. Methods Bone mineral density （ BMD） was measured using a dual-energy X-ray absorptiometry （ DXA） . Total genomic DNA was isolated from peripheral blood of all 11 family members and normal controls. The 11 gene mutations associated with osteopetrosis were excluded by gene sequencing. Genome-wide scan,fine mapping study and haplotype analysis were performed to identify the critical region. TRAP staining was used for observing the osteoclast formation in bone biopsy. Results There is no known gene mutation associated with this Chinese family with autosomal recessive osteopetrosis. The results of genome-wide scan,fine mapping study and haplotype analysis indicated that a single critical region of homozygosity on chromosome 19q13. 2q13. 3 between D19S197 and D19S545 spanning 8. 36 cM with maximum LOD score of 2. 907 at θ = 0 was identified. TRAP staining of bone specimen suggests the iliac crest of osteopetrosis patients have fewer osteoclasts than age and gender-matched normal subjects. Conclusion This study showed the decreased osteoclasts in the Chinese family with autosomal recessive osteopetrosis. There susceptible gene for osteopetrosis located on chromosome 19q13. 2-q13. 3,which is a novel autosomal recessive osteopetrosis that has never been reported.
出处
《中华骨质疏松和骨矿盐疾病杂志》
2013年第2期95-101,共7页
Chinese Journal Of Osteoporosis And Bone Mineral Research
基金
国家自然科学基金(81070696)
