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

特发性脊柱侧凸的发病机制尚不清楚，特发性脊柱侧凸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。同卵双胞胎特发性脊柱侧凸的一致性为92.3%，异卵双胞胎为66.7%。评估受影响的同卵对、异卵对和兄弟姐妹对曲率模式的一致性、曲线严重程度的对间差异和后凸畸形的对间差异。在曲度模式的一致性和曲度对间差异方面，单合子、异合子和兄弟姐妹间差异不显著。但三种组间后凸程度差异有统计学意义（Kruskal-Wallis检验，p<0.05）。连锁分析是研究遗传病与候选基因相关性的最佳方法之一。为了确认特发性脊柱侧凸的疾病基因，使用连锁分析的候选基因方法进行了测试。导致成骨不全症、ehers - danlos综合征、Stickler综合征、Marfan综合征、Beals综合征和Recklinghausen病的疾病基因被认为是特发性脊柱侧凸的候选基因。分离分析COL1A1、COL1A2、COL2A1、Fibrillin 1、Fibrillin 2和NF1，对3个大于13个个体的大家系进行分离分析。从外周血中提取个体dna，利用接近每个候选基因的微卫星标记进行PCR （q=0）。将每个标记的基因型输入到LINKAGE计算机打包程序中计算LOD分数。

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.