Genetic linkage studies in two families with the Stickler syndrome have been performed using restriction fragment length polymorphisms associated with the structural gene for type II collagen, COL2A1.
In a third AO family, however, recombination between AO and COL2A1 occurred in at least one meiosis, and the data were inconclusive with respect to linkage.
Linkage analysis with restriction fragment length polymorphisms for the gene for type II procollagen (COL2A1) was carried out in a family with the Stickler syndrome, or arthro-ophthalmopathy, an autosomal dominant disorder that affects the eyes, ears, joints, and skeleton.
Linkage analysis with restriction fragment length polymorphisms for the gene for type II procollagen (COL2A1) was carried out in a family with the Stickler syndrome, or arthro-ophthalmopathy, an autosomal dominant disorder that affects the eyes, ears, joints, and skeleton.
Four affected members of a family with Stickler syndrome were found to have a single base-pair deletion resulting in a translational frameshift in exon 40 of the procollagen II (COL2A1) gene on chromosome 12.
No basic defect has been found in patients with Kniest dysplasia, whereas Stickler dysplasia is one of four chondrodysplasias for which mutations of type II procollagen gene (COL2A1) have been identified.
Comparison with previously reported mutations suggested that mutations introducing premature termination codons in the COL2A1 gene are a frequent cause of the Stickler syndrome, but mutations in the COL2A1 gene that replace glycine codons with codons for bulkier amino acid can produce a broad spectrum of disorders that range from lethal chondrodysplasias to a syndrome involving only ocular tissues, similar to the syndrome in the family originally described by Wagner in 1938.
Since COL11A2 has also been localized to this chromosome region, a mutation in this collagen gene is an attractive explanation for the Stickler syndrome phenotype in this family.
We report what we believe is the first premature stop codon in the globular C-propeptide region encoded by the COL2A1 gene, in a family affected with Stickler syndrome.
However, both disorders have associated retinal pigment epithelial changes, poor night vision, visual field defects, and abnormal electroretinographic findings, which are not found in families with COL2A1-associated Stickler syndrome.
A mutation in COL11A2, the gene for alpha 2 (XI) procollagen, has recently been found in a family described as having Stickler syndrome, although there was no ocular involvement.