Marshall Syndrome Associated with a Splicing Defect at the COL11A1 Locus

SummaryMarshall syndrome is a rare, autosomal dominant skeletal dysplasia that is phenotypically similar to the more common disorder Stickler syndrome. For a large kindred with Marshall syndrome, we demonstrate a splice-donor–site mutation in the COL11A1 gene that cosegregates with the phenotype. The G+1→A transition causes in-frame skipping of a 54-bp exon and deletes amino acids 726–743 from the major triple-helical domain of the α1(XI) collagen polypeptide. The data support the hypothesis that the α1(XI) collagen polypeptide has an important role in skeletal morphogenesis that extends beyond its contribution to structural integrity of the cartilage extracellular matrix. Our results also demonstrate allelism of Marshall syndrome with the subset of Stickler syndrome families associated with COL11A1 mutations