Genetic analysis of structural elastic fiber and collagen genes in familial adolescent idiopathic scoliosis

Adolescent idiopathic scoliosis is a genetic disorder of unknown etiology. Scoliosis is a clinical feature of inherited connective-tissue disorders including Marfan syndrome. Mutations within the gene of FBN1 (fibrillin 15), a component of the extracellular matrix, are now linked to Marfan syndrome and similar clinical phenotypes. This study investigated the potential association of structural genes encoding for extracellular matrix components of FBN1, elastin, and one of the polypeptides of type-I collagen (COL1A2) with familial adolescent idiopathic scoliosis. Eleven pedigrees, including 96 individuals, were identified in which adolescent idiopathic scoliosis segregated in an apparent autosomal dominant pattern. Fifty-two individuals were determined to be affected with scoliosis. Genomic DNA was analyzed by genetic linkage utilizing four intragenic markers for the structural genes of FBN1, elastin, and COL1A2. Collectively, our results exclude the structural genes of FBN1, elastin, and COL1A2 as candidate genes within these families. However, when viewed individually, specific markers cannot be excluded within all of the families. This information complements previously reported data that fibrillin production and matrix incorporation from scoliotic fibroblasts in vitro are normal in more than 80% of patients studied.