GENETIC-ANALYSIS OF STRUCTURAL ELASTIC FIBER AND COLLAGEN GENES IN FAMILIAL ADOLESCENT IDIOPATHIC SCOLIOSIS

Adolescent idiopathic scoliosis is a genetic disorder of unknown etiol ogy. Scoliosis is a clinical feature of inherited connective-tissue di sorders 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 invest igated the potential association of structural genes encoding for extr acellular matrix components of FBN1, elastin, and one of the polypepti des of type-I collagen (COL1A2) with familial adolescent idiopathic sc oliosis. Eleven pedigrees, including 96 individuals, were identified i n which adolescent idiopathic scoliosis segregated in an apparent auto somal dominant pattern. Fifty-two individuals were determined to be af fected with scoliosis. Genomic DNA was analyzed by genetic linkage uti lizing four intragenic markers for the structural genes of FBN1, elast in, 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 exclud ed 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 patient s studied.