Spondyloepiphyseal dysplasia congenita: genetic linkage to type II collagen (COL2AI).

Abstract

Spondyloepiphyseal dysplasia congenita (SEDC) is an autosomal dominantly inherited chondrodysplasia characterized by disproportionate short stature (short trunk), abnormal epiphyses, and flattened vertebral bodies. Manifestations are present at birth. We ascertained a 4-generation family exhibiting the clinical manifestations of the disorder. Previous evidence suggesting defects of type II collagen associated with the SEDC phenotype led us to genotype the family for various COL2A1 gene-associated RFLPs. A total of 17 affected and unaffected members of this family were studied. The family was informative for a recently discovered HinfI RFLP. No recombinants between the marker and the phenotype were found in eight informative meioses. A maximum LOD score of 3.01 was obtained at a recombination fraction of .00. Our results indicate that the SEDC phenotype in this family is caused by mutations in or very close to the COL2A1 locus.