Autosomal recessive Stickler syndrome in two families is caused by mutations in the COL9A1 gene

textabstractPurpose. To investigate COL9A1 in two families suggestive of autosomal recessive Stickler syndrome and to delineate the associated phenotype. Methods. The probands of two consanguineous autosomal recessive Stickler families were evaluated for homozygosity using SNP microarray in one and haplotype analysis in the other. Subsequently, the entire COL9A1 open reading frame was analyzed by DNA sequencing in all members of the respective families. Several family members were investigated for dysmorphic features as well as ophthalmic, audiologic, and radiologic abnormalities. Results. A novel homozygous COL9A1 mutation (p.R507X) was identified in two affected Turkish sisters, and the previously published mutation (p.R295X) was found in a Moroccan boy. Ophthalmic assessment revealed myopia, cataracts, distinct vitreous changes, progressive chorioretinal degeneration, and exudative and rhegmatogenous retinal detachments. All three had sensorineural hearing loss and epiphyseal dysplasia. Intervertebral disc bulging was observed in one patient and in two heterozygous carriers of the p.R507X mutation. Conclusions. A second, novel mutation was identified in COL9A1, causing autosomal recessive Stickler syndrome together with the previously described nucleotide change in two separate families. Although the overall phenotype was comparable to autosomal dominant Stickler, vitreous changes that may enable recognition of patients who are likely to carry mutations in COL9A1 were identified, and exudative retinal detachment was observed as a new finding in Stickler syndrome