title: Identification of a stop codon mutation in exon 2 of the collagen 2A1 gene in a large stickler syndrome family.
abstract: OBJECTIVE
  To describe the clinical features and identify the mutation responsible for an autosomal dominant vitreoretinal degeneration occurring in a previously unreported large family.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Family members were evaluated clinically over a 30-year period. Genealogical investigation, genetic linkage to known vitreoretinal degenerations, and mutation screening of the COL2A1 gene were performed.
  
  
  RESULTS
  We identified a single large family (2,384 total family members) with vitreoretinal degeneration spanning 12 generations. We reviewed the clinical records of 165 family members (95 affected and 70 unaffected). The common clinical findings in affected individuals included early-onset posterior perivascular retinal degeneration, vitreous degeneration, and retinal detachment. The incidence of retinal detachment was 57% (95/165) and the mean age of onset was 15.2 years. Orofacial, skeletal, and auditory abnormalities were seen in 0%, 5%, and 7.5%, respectively, in a subset of 28 affected subjects. Linkage to the collagen COL2A1 locus was demonstrated and a cytosine to adenosine transition identified within exon 2, leading to the creation of a stop codon at position 86 (Cys86Stop).
  
  
  CONCLUSIONS
  Identification of the mutation in this family enables diagnosis of individuals at risk for potentially blinding complications in this condition at an early age. Given the variability of the Stickler phenotype, mutation detection allows for more comprehensive genetic counseling and directs clinical monitoring to family members inheriting the disease gene.
authors.affiliation: Henry and Corinne Bower Laboratory, Wills Eye Hospital, Philadelphia, Pennsylvania 19107, USA. ldonoso@vision-research.org
authors.forename: Larry A
authors.initials: LA
authors.lastname: Donoso
authors.forename: Albert O
authors.initials: AO
authors.lastname: Edwards
authors.forename: Arcilee T
authors.initials: AT
authors.lastname: Frost
authors.forename: Robert
authors.initials: R
authors.lastname: Ritter
authors.forename: N Nina
authors.initials: NN
authors.lastname: Ahmad
authors.forename: Tamara
authors.initials: T
authors.lastname: Vrabec
authors.forename: Jerry
authors.initials: J
authors.lastname: Rogers
authors.forename: David
authors.initials: D
authors.lastname: Meyer
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018388:Codon, Terminator / Q000235:genetics*; D015331:Cohort Studies; D024043:Collagen Type II / Q000235:genetics*; D003240:Connective Tissue Diseases / Q000175:diagnosis / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D015785:Eye Diseases, Hereditary / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics*; D012163:Retinal Detachment / Q000175:diagnosis / Q000235:genetics; D017422:Sequence Analysis, DNA; D013577:Syndrome; D014822:Vitreous Body / Q000473:pathology*
chemical_list: C499177:COL2A1 protein, human; D018388:Codon, Terminator; D024043:Collagen Type II