Study on the pathogenesis of idiopathic scoliosis using linkage analysis for the familiar scoliotic patients.

特发性脊柱侧弯的发病机制尚不清楚，特发性脊柱侧弯也没有一致的病理改变。然而，有强有力的证据表明，遗传因素在这种情况下起到了作用。DNA指纹图谱显示有13对同卵双胞胎和9对异卵双胞胎。同卵双生子特发性脊柱侧凸的符合率为92.3%，异卵双生子为66.7%。对受影响的单合子配对、双合子配对和同胞配对的曲度模式的一致性、弯曲严重程度的组间差异和后凸的组间差异进行了评估。至于曲度模式的一致性和曲度严重程度的配对差异，单合子、双合子和同胞之间没有显著差异。然而，3种配对的后凸畸形有显著差异(Kruskal-Wallis检验，p&lt；0.05)，连锁分析是检测遗传病与候选基因关联的最好方法之一。为了确定特发性脊柱侧凸的致病基因，我们测试了一种使用连锁分析的候选基因方法。导致成骨发育不全、Ehler-Danlos综合征、Stickler综合征、Marfan综合征、Beals综合征和Reckinghausen病的疾病基因被认为是特发性脊柱侧凸的候选基因。对3个包含13个以上个体的家系进行了COL1A1、COL1A2、COL2A1、纤维蛋白1、纤维蛋白2和NF1的分离分析。从外周血中提取单个DNA，利用每个候选基因附近的微卫星标记进行聚合酶链式反应(Q=0)。将每个标记的基因型别输入LINK计算机程序，计算LOD评分。

The pathogenesis of idiopathic scoliosis remains unclear, and no consistent pathological changes specific to idiopathic scoliosis have been demonstrated. However, there is strong evidence that genetic factors play a role in this condition. DNA fingerprints revealed that there were 13 monozygotic and 9 dizygotic pairs of twins. Concordance for idiopathic scoliosis among monozygotic twins was 92.3%, while among dizygotic twins it was 66.7%. Affected monozygotic pairs, dizygotic pairs, and sib pairs were evaluated for concordance for pattern of curvature, interpair differences in curve severity, and interpair differences in kyphosis. As for concordance for pattern of curvature and interpair differences in curve severity, There were not significant differences among monozygotes, dizygotes, and sibs. However, there were significant differences in kyphosis among 3 kinds of pairs (Kruskal-Wallis test ; p<0.05).Linkage analysis is one of the best methods for examining the association of the genetic diseases with candidate genes. To confirm disease genes for idiopathic scoliosis, a candidate gene approach using linkage analysis was tested. Disease genes causing Osteogenesis Imperfecta, Ehlers-Danlos syndrome, Stickler syndrome, Marfan syndrome, Beals syndrome, and Recklinghausen disease were considered candidate genes for idiopathic scoliosis. Segregation analysis of COL1A1, COL1A2, COL2A1, Fibrillin 1, Fibrillin 2, and NF1 was performed for 3 large pedigrees consisting of more than 13 individuals. Individual DNAs were extracted from peripheral blood, and PCR was perfomed using microsatellite markers close to each candidate gene (q=0). Genotypes of each marker were inputted into the LINKAGE computer package program to calculate LOD scores.