title: A loss of function mutation in the COL9A2 gene causes autosomal recessive Stickler syndrome.
abstract: Stickler syndrome is characterized by ocular, auditory, skeletal, and orofacial abnormalities. We describe a family with autosomal recessive Stickler syndrome. The main clinical findings consisted of high myopia, vitreoretinal degeneration, retinal detachment, hearing loss, and short stature. Affected family members were found to have a homozygous loss-of-function mutation in COL9A2, c.843_c.846 + 4del8. A family with autosomal recessive Stickler syndrome was previously described and found to have a homozygous loss-of-function mutation in COL9A1. COL9A1, COL9A2, and COL9A3 code for collagen IX. All three collagen IX α chains, α1, α2, and α3, are needed for formation of functional collagen IX molecule. In dogs, two causative loci have been identified in autosomal recessive oculoskeletal dysplasia. This dysplasia resembles Stickler syndrome. Recently, homozygous loss-of-function mutations in COL9A2 and COL9A3 were found to co-segregate with the loci. Together the data from the present study and the previous studies suggest that loss-of-function mutations in any of the collagen IX genes can cause autosomal recessive Stickler syndrome.
authors.affiliation: Connective Tissue Gene Tests, Allentown, Pennsylvania 18106, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Baker
authors.forename: Carol
authors.initials: C
authors.lastname: Booth
authors.forename: Corrine
authors.initials: C
authors.lastname: Fillman
authors.forename: Michael
authors.initials: M
authors.lastname: Shapiro
authors.forename: Michael P
authors.initials: MP
authors.lastname: Blair
authors.forename: James C
authors.initials: JC
authors.lastname: Hyland
authors.forename: Leena
authors.initials: L
authors.lastname: Ala-Kokko
mesh_terms: D000328:Adult; D001168:Arthritis / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D024081:Collagen Type IX / Q000235:genetics*; D003240:Connective Tissue Diseases / Q000235:genetics* / Q000473:pathology; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012163:Retinal Detachment / Q000235:genetics* / Q000473:pathology
chemical_list: C120282:COL9A2 protein, human; D024081:Collagen Type IX