Molecular characteristics

The conditions associated with defects in the COL27A1 gene are inherited in an autosomal recessive manner and are caused by biallelic loss of function or hypomorphic variation in COL27A1. The protein product of COL27A1 is collagen XXVII, a fibrillar collagen produced mainly by chondrocytes and important for the composition and appropriate layout of the extracellular matrix during skeletogenesis.

Steel syndrome is a clinical and molecular entity characterized by homozygosity for the missense p.Gly697Arg variant in COL27A1, mainly in patients of Puerto Rican ancestry. The p.Gly697Arg variant is a founder mutation that appears to have arisen in the Caribbean region 9 to 14 generations ago. Other variants reported in patients with COL27A1 associated osteochondrodysplasias include nonsense, splicing, and frameshift mutations.