title: Mutation in collagen II alpha 1 isoforms delineates Stickler and Wagner syndrome phenotypes.
abstract: OBJECTIVE
  Stickler syndrome is an arthro-ophthalmopathy with phenotypic overlap with Wagner syndrome. The common Stickler syndrome type I is inherited as an autosomal dominant trait, with causal mutations in collagen type II alpha 1 (COL2A1). Wagner syndrome is associated with mutations in versican (VCAN), which encodes for a chondroitin sulfate proteoglycan. A three-generation Caucasian family variably diagnosed with either syndrome was screened for sequence variants in the COL2A1 and VCAN genes.
  
  
  METHODS
  Genomic DNA samples derived from saliva were collected from all family members (six affected and four unaffected individuals). Complete sequencing of COL2A1 and VCAN was performed on two affected individuals. Direct sequencing of remaining family members was conducted if the discovered variants followed segregation.
  
  
  RESULTS
  A base-pair substitution (c.258C>A) in exon 2 of COL2A1 cosegregated with familial disease status. This known mutation occurs in a highly conserved site that causes a premature stop codon (p.C86X). The mutation was not seen in 1,142 ethnically matched control DNA samples.
  
  
  CONCLUSIONS
  Premature stop codons in COL2A1 exon 2 lead to a Stickler syndrome type I ocular-only phenotype with few or no systemic manifestations. Mutation screening of COL2A1 exon 2 in families with autosomal dominant vitreoretinopathy is important for accurate clinical diagnosis.
authors.affiliation: Duke Center for Human Genetics, 905 S LaSalle Street, 27705, Durham, North Carolina 27710, USA.
authors.forename: Khanh-Nhat
authors.initials: KN
authors.lastname: Tran-Viet
authors.forename: Vincent
authors.initials: V
authors.lastname: Soler
authors.forename: Valencia
authors.initials: V
authors.lastname: Quiette
authors.forename: Caldwell
authors.initials: C
authors.lastname: Powell
authors.forename: Tammy
authors.initials: T
authors.lastname: Yanovitch
authors.forename: Ravikanth
authors.initials: R
authors.lastname: Metlapally
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Luo
authors.forename: Nicholas
authors.initials: N
authors.lastname: Katsanis
authors.forename: Erica
authors.initials: E
authors.lastname: Nading
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001168:Arthritis / Q000235:genetics*; D001483:Base Sequence; D024043:Collagen Type II / Q000235:genetics* / Q000378:metabolism; D003240:Connective Tissue Diseases / Q000235:genetics*; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D005190:Family; D005260:Female; D005786:Gene Expression Regulation; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics*; D012163:Retinal Detachment / Q000235:genetics*; D053675:Versicans / Q000172:deficiency
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II; D018076:DNA, Complementary; D020033:Protein Isoforms; D053675:Versicans