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

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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.