A family with Stickler syndrome type 2 has a mutation in the COL11A1 gene resulting in the substitution of glycine 97 by valine in alpha 1 (XI) collagen

Stickler syndrome (hereditary arthro-ophthalmopathy) is the commonestinherited cause of retinal detachment and one of the commonest autosomaldominant connective tissue dysplasias. There is clinical and locusheterogeneity with about two thirds of families linked to the gene encodingtype II procollagen (COL2A1). Families with Sticklers syndrome type 1 havea characteristic congenital vitreous anomaly and are linked withoutrecombination to markers at the COL2A1 locus. In contrast families with thetype 2 variety have a different vitreo- retinal phenotype and are notlinked to the COL2A1 gene. Type XI collagen is a quantitatively minorfibrillar collagen related to type V collagen and associated with the moreabundant type II collagen fibrils. A mutation in COL11A2, the gene foralpha 2 (XI) procollagen, has recently been found in a family described ashaving Stickler syndrome, although there was no ocular involvement. Here weshow for the first time that a family with the full Type 2 Sticklersyndrome including vitreous and retinal abnormalities is linked to theCOL11A1 gene and characterise the mutation as a Glycine to Valinesubstitution at position 97 of the triple helical domain caused by a singlebase G-- >T mutation. These results are the first to provideconfirmation that type XI collagen is an important structural component ofhuman vitreous. They also support previous work suggesting that mutationsin the genes encoding collagen XI can give rise to some manifestations ofStickler syndrome, but of these, only mutations in COL11A1 will give thefull syndrome including the vitreo-retinal features.